Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

acute myocardial infarction or unstable angina

1st line – coronary intervention and medical management

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INITIAL
|
acute myocardial infarction or unstable angina
1st line – 

coronary intervention and medical management

For people with ST-elevation myocardial infarction (STEMI) and ischemic symptoms for <12 hours, primary percutaneous coronary intervention (PCI) is recommended to improve survival.[339] Primary PCI is superior to fibrinolytic therapy and fibrinolytic therapy is therefore only recommended if PCI is not immediately available (i.e., within 120 minutes).[339] An analysis of data from 11 clinical trials compared PCI with fibrinolytic therapy in 2725 patients with STEMI, including 367 patients with diabetes.[342]​ Among patients with diabetes, 30-day mortality or nonfatal reinfarction rate was 19.3% for those treated with fibrinolytics and 9.2% for those who underwent primary PCI. If onset of ischemic symptoms is ≥12 hours and the patient is in cardiogenic shock or experiencing hemodynamic instability, primary PCI is indicated, or coronary artery bypass graft (CABG) if PCI is not feasible.[339] PCI may also be reasonable in patients who are stable and presenting 12-24 hours after symptom onset, as well as in those whose STEMI is complicated by ongoing ischemia, acute severe heart failure, or life-threatening arrhythmia.[339] 

Non-ST-elevation acute coronary syndrome (NSTE-ACS) most commonly manifests as non-ST-elevation MI (NSTEMI) but may also present as unstable angina.​[144]​ Immediate invasive strategy (coronary angiography with intent of revascularization) is required in patients with NSTEMI and cardiogenic shock, refractory angina, or hemodynamic/electrical instability.[339] Early invasive strategy (usually within 24 hours) is recommended for patients at high risk for cardiovascular (CV) events: for example, those with a high Global Registry of Acute Coronary Events (GRACE) score. Patients with low- or intermediate-risk NSTEMI should undergo coronary angiography before discharge with the intent of revascularization. Invasive strategy is important in NSTEMI as it will help determine the suitability for revascularization and the appropriate mode (PCI vs. CABG).[339]

All patients with STEMI or NSTEMI (i.e., acute coronary syndromes [ACS]) should receive aspirin and an oral P2Y12 inhibitor (e.g., clopidogrel, prasugrel, ticagrelor).[338]​ Clinicians should also consider beta-blockers, nitrates, and ACE inhibitors as part of comprehensive early management.[338]​​

For more comprehensive information on the acute management of these conditions, see ST-elevation myocardial infarction, Non-ST-elevation myocardial infarction, and Unstable angina.

Uncontrolled blood glucose levels in the perioperative or periprocedural period are associated with adverse outcomes for patients with diabetes. Good glycemic control is linked to shorter hospital stays, reduced likelihood of readmission, and improved postoperative survival rates.[29]​ ​However, trials of tight glycemic control in critically ill patients have yielded mixed results.[371][372]​​ In one study of acute coronary syndrome patients who presented with hyperglycemia, intensive glucose control was associated with harm and did not reduce infarct size.[308] A large randomized controlled trial also raised questions about the value of intensive inpatient blood glucose targets, reporting lower mortality in intensive care unit (ICU) patients treated to a conventional blood glucose target of ≤180 mg/dL (≤10 mmol/L)compared with those treated to a much tighter target range of 81 to 108 mg/dL (4.5 to 6.0 mmol/L).[309] These findings raise concen about whether lowering blood glucose below approximately 140 to 180 mg/dL (7.8 to 10.0 mmol/L) provides any additional benefit in the ICU setting.[310] In contrast, a randomized controlled of hyperglycemic (glucose ≥140 mg/dL [≥7.8 mmol/L]) patients with STEMI undergoing early PCI found that intensive periprocedural glycemic control led to a 50% reduction in restenosis at 6 months compared with conventional management.[343]

The American Diabetes Association (ADA) recommends that in critically ill patients, insulin therapy should be started for persistent hyperglycemia ≥180 mg/dL (≥10 mmol/L) (confirmed on two occasions within 24-hours).[29]​​ Once insulin therapy is started, a target glucose range of 140 to 180 mg/dL (7.8 to 10.0 mmol/L) is recommended for most patients.[29]​​ More stringent individualized goals may be appropriate for selected patients, as long as they can be achieved without significant hypoglycemia.[29]​​ Management should be guided by an intravenous insulin protocol with proven efficacy and safety in achieving glucose targets without increasing the risk of severe hypoglycemia.[29]​​​

ACUTE

highly significant coronary artery disease: without acute myocardial infarction or unstable angina

1st line – coronary artery bypass graft and perioperative tight glycemic control

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ACUTE
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highly significant coronary artery disease: without acute myocardial infarction or unstable angina
|
left main stenosis
1st line – 

coronary artery bypass graft and perioperative tight glycemic control

The 2021 American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions coronary artery revascularization guidelines recommend coronary artery bypass graft (CABG) for left main disease.[339] However, they recognize that it is reasonable to consider PCI in patients with low- or intermediate-complexity disease in the rest of the coronary anatomy.[339]

Intravenous insulin infusion provides more reliable absorption and allows for rapid titration compared with subcutaneous injection. In the perioperative period for CABG, effective glucose control may reduce the risk of infectious complications (including sternal wound infection and mediastinitis), lower cardiac mortality due to pump failure, and decrease the incidence of supraventricular tachycardia.infectious complications, such as sternal wound infections and mediastinitis, cardiac mortality caused by pump failure, and the risk of supraventricular tachycardia.[311][312][313]

1st line – revascularization and perioperative tight glycemic control

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ACUTE
|
highly significant coronary artery disease: without acute myocardial infarction or unstable angina
|
multivessel coronary artery disease
1st line – 

revascularization and perioperative tight glycemic control

Patients with diabetes and complex multivessel coronary artery disease (CAD) should undergo a multidisciplinary heart-team approach to revascularization, inclusive of an interventional cardiologist and a cardiac surgeon.[339]

Either percutaneous coronary intervention (PCI) with drug-eluting stents or coronary artery bypass graft (CABG) may be suitable depending on factors such as anatomic location of lesions, lesion length, presence of chronic total occlusions, left ventricular function, and comorbidity. CABG is generally recommended in preference to PCI to improve survival in patients with diabetes and multivessel CAD in whom mechanical revascularization is likely to improve survival.[339][345][346]​​ This is particularly recommended if a left internal mammary artery to left anterior descending artery (LIMA-LAD) graft is used and the patient is a good surgical candidate.[339]

Intravenous insulin infusion provides more reliable absorption and allows for rapid titration compared with subcutaneous injection. In the perioperative period for CABG, effective glucose control may reduce the risk of infectious complications (including sternal wound infection and mediastinitis), lower cardiac mortality due to pump failure, and decrease the incidence of supraventricular tachycardia.[311][312][313]

1st line – medical management

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ACUTE
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highly significant coronary artery disease: without acute myocardial infarction or unstable angina
|
single-vessel coronary artery disease
1st line – 

medical management

In stable patients with single-vessel disease and no recent acute coronary syndrome or left ventricular dysfunction, the initial treatment is conservative and involves guideline-directed medical therapy for coronary artery disease. This may include antihypertensive agents, lipid-lowering agents, and antiplatelet therapy.[314]​ When optimized, medical therapy has demonstrated similar outcomes to revascularization.[364][365]​ This approach needs patient-physician discussion to tailor therapy based on symptoms, response to therapy, available expertise, and patient preference.

Consider – revascularization and perioperative tight glycemic control

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ACUTE
|
highly significant coronary artery disease: without acute myocardial infarction or unstable angina
|
single-vessel coronary artery disease
Consider – 

revascularization and perioperative tight glycemic control

Treatment recommended for SOME patients in selected patient group

The usefulness of coronary revascularization in improving survival is uncertain in patients with single-vessel disease involving the proximal left anterior descending artery with normal left ventricular function.[339]

Revascularization may be considered after patient-physician discussion as well as heart team discussion in regards to utility and timing.[339] 

Coronary revascularization also has an important role in patients who are symptomatic with angina refractory to maximal medical therapy.[339]

If revascularization is indicated, and the anatomy is amenable to percutaneous coronary intervention (PCI), PCI is preferred over coronary artery bypass graft (CABG) for single-vessel coronary artery disease.[339][345]

Intravenous insulin infusion provides more reliable absorption and allows for rapid titration compared with subcutaneous injection. In the perioperative period of CABG, effective glucose control may reduce the risk of infectious complications (including sternal wound infection and mediastinitis), lower cardiac mortality due to pump failure, and decrease the incidence of supraventricular tachycardia.[312][313]

ONGOING

diabetic cardiovascular disease: stable and/or after intervention

1st line – ACE inhibitor or angiotensin-II receptor antagonist

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ONGOING
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diabetic cardiovascular disease: stable and/or after intervention
1st line – 

ACE inhibitor or angiotensin-II receptor antagonist

European Society of Cardiology and American Heart Association (AHA)/American College of Cardiology guidelines recommend use of an ACE inhibitor (or an angiotensin-II receptor antagonist if an ACE inhibitor is contraindicated or not tolerated) in patients with chronic coronary disease and diabetes, even in the absence of hypertension, to reduce cardiovascular risk, particularly in those with heart failure (HF) or chronic kidney disease (CKD).[6][314][315]

In contrast, the American Diabetes Association (ADA) adopts a more targeted strategy, recommending ACE inhibitors or angiotensin-II receptor antagonists primarily for patients with diabetes and hypertension who either have established atherosclerotic cardiovascular disease (CVD) or are age ≥55 years with additional CVD risk factors.[29] The ADA also strongly recommends ACE inhibitors or angiotensin-II receptor antagonists for the treatment of hypertension in patients with diabetes and CKD, particularly those with albuminuria (urinary albumin-to-creatinine ratio ≥30 mg/g), to reduce the risk of CKD progression and cardiovascular events.[29] It also recommends that one of these drugs should be offered to patients with diabetes and symptomatic (stage C) HF to reduce morbidity and mortality, and to those with asymptomatic (stage B) HF to reduce the risk of progression to symptomatic HF.[29]

ACE inhibitors and angiotensin-II receptor antagonists should not be used in combination due to increased risk for acute kidney injury and hyperkalemia.[29]​​​[318]​​ A dose reduction may be required in patients with renal impairment. ACE inhibitors have also shown increased risk for hypoglycemia in conjunction with insulin or insulin secretagogue (sulfonylurea or meglitinide).[319]

Serum creatinine, estimated glomerular filtration rate (eGFR), and potassium should be checked within 7-14 days of initiation of treatment with an ACE inhibitor or angiotensin-II receptor antagonist, as well as following uptitration of dose and then at least subsequent routine appointments.[29]​​

Primary options

lisinopril: 5 mg orally once daily initially, increase gradually according to response, maximum 40 mg/day

OR

enalapril: 2.5 mg orally twice daily initially, increase gradually according to response, maximum 40 mg/day

OR

captopril: 6.25 mg orally three times daily initially, increase gradually according to response, maximum 150 mg/day

Secondary options

candesartan cilexetil: 4 mg orally once daily initially, increase gradually according to response, maximum 32 mg/day

OR

irbesartan: 75 mg orally once daily initially, increase gradually according to response, maximum 300 mg/day

OR

losartan: 25-50 mg orally once daily initially, increase gradually according to response, maximum 150 mg/day

OR

valsartan: 40 mg orally twice daily initially, increase gradually according to response, maximum 320 mg/day

Consider – additional antihypertensive therapy

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ONGOING
|
diabetic cardiovascular disease: stable and/or after intervention
Consider – 

additional antihypertensive therapy

Treatment recommended for SOME patients in selected patient group

The American Diabetes Association (ADA) recommends an individualized approach to blood pressure (BP) management, with consideration of antihypertensive drug therapy for all nonpregnant patients with diabetes whose BP is persistently elevated above ≥130/80 mmHg. Guidelines recommend a target goal of <130/80 mmHg for nonpregnant people with diabetes, providing this can be safely attained.[6][29]​​​​[60][61]

The ADA recommends starting one antihypertensive agent for patients with initial BP ≥130/80 and <150/90 mmHg, and starting two antihypertensive agents for those with initial BP ≥150/90 mmHg.[29]​ ​For patients with diabetes who have coronary artery disease (CAD) or chronic kidney disease (CKD) and/or albuminuria (eGFR <60 mL/minute/1.73 m², urinary albumin-to-creatinine ratio ≥30 mg/g creatinine), initial antihypertensive therapy should be with an ACE inhibitor, or an angiotensin-II receptor antagonist if an ACE inhibitor is not tolerated (a dose reduction may be required in patients with renal impairment). However, additional antihypertensive agents may be required.

For those whose BP is ≥150/90 mmHg, a calcium-channel blocker (e.g., amlodipine, felodipine, nifedipine) or a thiazide diuretic (e.g., hydrochlorothiazide) should be considered in addition at treatment initiation.[29]​​

Beta-blockers (e.g., metoprolol, bisoprolol, carvedilol) may be appropriate to improve outcomes as antihypertensive agents in patients with prior myocardial infarction (MI), active angina, atrial fibrillation with rapid ventricular response, or heart failure with reduced ejection fraction.[29]​​ These patients are typically started on beta-blockers alone, with other antihypertensive therapies added as needed. If a beta-blocker is indicated, an agent should be selected that has concomitant vasodilatory effects to reduce potential for adverse metabolic impact.[115]​ Beta-blockers may mask symptoms of hypoglycemia and also have the potential to exacerbate hypoglycemic episodes, particularly when used concurrently with sulfonylureas.[29]​​[322][323]

Multiple drug therapy is often required to achieve antihypertensive targets.[29]​​​ If BP remains uncontrolled on monotherapy, add an agent from a different first-line class.[29]​​​ If BP remains uncontrolled despite combination therapy with first-line agents (i.e., three classes of antihypertensive drugs including a diuretic, plus lifestyle modifications), discontinue or minimize interfering substances such as nonsteroidal anti-inflammatory drugs (NSAIDs), evaluate for secondary causes of hypertension (including obstructive sleep apnea), and consider the addition of an aldosterone antagonist (e.g., spironolactone, eplerenone).[29]​​​[115]​​ Referral to a hypertension specialist may also be necessary.[29]​​​[115]​ The number of antihypertensive therapies required will vary between patients and is dependent on their clinical situation and tolerance.

People with diabetes and hypertension should monitor their BP at home in addition to having it checked regularly in the clinic setting.[29]​​​

Serum creatinine/eGFR and potassium should be checked within 7-14 days of initiation of treatment with an aldosterone antagonist or diuretic, as well as following uptitration of dose, and then on a regular basis at subsequent routine appointments.[29]​​

Primary options

hydrochlorothiazide: 12.5 to 25 mg orally once daily initially, increase gradually according to response, maximum 50 mg/day

-- AND / OR --

amlodipine: 2.5 mg orally once daily initially, increase gradually according to response, maximum 10 mg/day

or

felodipine: 2.5 mg orally once daily initially, increase gradually according to response, maximum 10 mg/day

or

nifedipine: 30-60 mg orally (extended-release) once daily initially, increase gradually according to response, maximum 90 mg/day

-- AND / OR --

metoprolol tartrate: 50 mg orally (immediate-release) twice daily initially, increase gradually according to response, maximum 450 mg/day

or

bisoprolol: 2.5 to 5 mg orally once daily initially, increase gradually according to response, maximum 20 mg/day

or

carvedilol: 6.25 mg orally (immediate-release) twice daily initially, increase gradually according to response, maximum 50 mg/day

-- AND / OR --

spironolactone: 25-100 mg/day orally given in 1-2 divided doses

or

eplerenone: 50 mg orally once or twice daily

Plus – lipid management

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ONGOING
|
diabetic cardiovascular disease: stable and/or after intervention
Plus – 

lipid management

Treatment recommended for ALL patients in selected patient group

For patients with diabetes and established atherosclerotic cardiovascular disease (ASCVD), both US and European guidelines recommend a low-density lipoprotein cholesterol (LDL-C) goal of <55 mg/dL (<1.42 mmol/L) and at least a 50% reduction from baseline.[6][29]​​[114]​​​

Statins are the first-line agent for pharmacologic treatment of dyslipidemia and may have additional therapeutic effects independent of lipid-lowering action.[29]​ Moderate-intensity statin therapy lowers LDL-C level by 30% to 50%, while high-intensity statin therapy lowers it by ≥50%.[114] Low-dose statin therapy is generally not recommended in people with diabetes, but it is sometimes the only dose of statin that an individual can tolerate.[29]​​

G​​​uidelines recommend high-intensity statin therapy in adults of all ages with diabetes and ASCVD.[29]​​[114] For people who do not tolerate the intended statin intensity, the maximum tolerated statin dose should be used.​​

Addition of ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor (e.g., evolocumab, alirocumab) is recommended if the LDL-C reduction goal is not achieved on maximum tolerated statin therapy.[29]​​

For people intolerant of statin therapy, a PCSK9 inhibitor, bempedoic acid, or inclisiran should be considered as alternative cholesterol-lowering therapies.[29]​​

A lipid profile should be checked: at initiation of statins or other lipid-lowering therapy; 4-12 weeks after initiation or a change in dose; and annually thereafter.[29]​​

Icosapent ethyl can be considered in patients with ASCVD (or other CV risk factors) who are on a statin at maximal dose and have controlled LDL-C but elevated triglycerides (150 to 499 mg/dL [1.7 to 5.6 mmol/L).[29]​ It has been shown to modestly reduce CV events.​​[115][116]​​​​

If triglyceride levels exceed 500 mg/dL (5.65 mmol/L), fibrate therapy may be beneficial to reduce the risk of pancreatitis.[115] Fibrates are most often added to statin therapy, although the ADA notes that this approach is generally not recommended due to a lack of evidence of improvement in CVD outcomes.[29]​​​ Furthermore, caution is recommended as combination statin and fibrate therapy can increase the risk of myositis and rhabdomyolysis. To lower the risk, fenofibrate is recommended over gemfibrozil.[47]

Primary options

atorvastatin: high intensity: 40-80 mg orally once daily

OR

rosuvastatin: high intensity: 20-40 mg orally once daily

OR

atorvastatin: high intensity: 40-80 mg orally once daily

or

rosuvastatin: high intensity: 20-40 mg orally once daily

-- AND --

ezetimibe: 10 mg orally once daily

OR

atorvastatin: high intensity: 40-80 mg orally once daily

or

rosuvastatin: high intensity: 20-40 mg orally once daily

-- AND --

evolocumab: 140 mg subcutaneously every 2 weeks; or 420 mg subcutaneously once monthly

or

alirocumab: 75-150 mg subcutaneously every 2 weeks; or 300 mg subcutaneously once monthly

OR

atorvastatin: high intensity: 40-80 mg orally once daily

or

rosuvastatin: high intensity: 20-40 mg orally once daily

-- AND --

ezetimibe: 10 mg orally once daily

-- AND --

evolocumab: 140 mg subcutaneously every 2 weeks; or 420 mg subcutaneously once monthly

or

alirocumab: 75-150 mg subcutaneously every 2 weeks; or 300 mg subcutaneously once monthly

Secondary options

bempedoic acid: 180 mg orally once daily

OR

inclisiran: 284 mg subcutaneously every 3 months for 2 doses, followed by 284 mg every 6 months

OR

evolocumab: 140 mg subcutaneously every 2 weeks; or 420 mg subcutaneously once monthly

OR

alirocumab: 75-150 mg subcutaneously every 2 weeks; or 300 mg subcutaneously once monthly

Tertiary options

atorvastatin: high intensity: 40-80 mg orally once daily

or

rosuvastatin: high intensity: 20-40 mg orally once daily

-- AND --

icosapent ethyl: 2 g orally twice daily

Plus – metformin

Back
ONGOING
|
diabetic cardiovascular disease: stable and/or after intervention
Plus – 

metformin

Treatment recommended for ALL patients in selected patient group

The hemoglobin A1c (HbA1c) goal for most nonpregnant adult patients is <7% (<53 mmol/mol) to optimize clinical outcomes, though targets should be individualized.[29]​ If using a continuous glucose monitoring (CGM) device to assess glycemia, a parallel goal is time in range >70%, with time below range <4% and time below 54 mg/dL (<3 mmol/L) <1%.[29]​​ Less stringent goals may be appropriate for very young children, older adults, people with a history of severe hypoglycemia, and those with limited life expectancies, advanced microvascular or macrovascular complications, or comorbid conditions.[29] If using CGM, the American Diabetes Association recommends a target of >50% time in range with <1% time below range for those with frailty or at high risk of hypoglycemia.​​[29]

Metformin is the most commonly used first-line drug for type 2 diabetes because of its effectiveness, safety, and low cost.[29]​​​​​ Evidence for the cardiovascular benefit of metformin is limited; however, it does not cause weight gain or hypoglycemia, and is widely available relative to other agents.[47]

Primary options

metformin: 500 mg orally (immediate-release) once daily initially, increase by 500 mg/day increments every week, maximum 1000 mg twice daily

Plus – glucagon-like peptide-1 (GLP-1) receptor agonist or tirzepatide and/or sodium-glucose cotransporter-2 (SGLT2) or SGLT1/SGLT2 inhibitor

Back
ONGOING
|
diabetic cardiovascular disease: stable and/or after intervention
Plus – 

glucagon-like peptide-1 (GLP-1) receptor agonist or tirzepatide and/or sodium-glucose cotransporter-2 (SGLT2) or SGLT1/SGLT2 inhibitor

Treatment recommended for ALL patients in selected patient group

For patients with established atherosclerotic cardiovascular disease (ASCVD), significant ASCVD risk factors, established heart failure (HF), or established chronic kidney disease (CKD), addition of a GLP-1 receptor agonist or a SGLT2 inhibitor is strongly recommended to reduce the risk of adverse cardiovascular (CV) or kidney events.[29]​​​[153][219]​​​​​

The American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) advise that for patients in whom ASCVD predominates (e.g., previous MI, unstable angina, ischemic stroke, or indicators of high CV risk present), either a GLP-1 receptor agonist or an SGLT2 inhibitor should be used for glycemic management and CV event reduction.[29]​​[220]​​​​ Although definitions of what constitutes high CV risk vary, most comprise ≥55 years of age with two or more additional risk factors such as obesity, hypertension, smoking, dyslipidemia, or albuminuria.[220] While the ADA and EASD do not specify different treatments based on specific ASCVD manifestations, the American College of Physicians and American Heart Association/American Stroke Association specify that GLP-1 receptor agonists should be prioritized in patients with an increased risk for stroke.[119][216]​​​​

For patients in whom CKD predominates (with confirmed estimated glomerular filtration rate [eGFR] 20-60 mL/min/1.73 m² and/or albuminuria), either an SGLT2 inhibitor or GLP-1 receptor agonist with demonstrated benefit in this population should be used for glycemic management, slowing progression of CKD, and reducing CV events.[29] In patients with advanced CKD (eGFR <30 mL/min/ 1.73 m²), a GLP-1 receptor agonist is preferred due to lower risk of hypoglycemia and for CV event reduction.[29]

For patients in whom HF (with either reduced ejection fraction [HFrEF] or preserved ejection fraction [HFpEF]) predominates, SGLT2 inhibitors should usually be favored for both glycemic management and prevention of HF hospitalization.[29][220][216] However, in patients with symptomatic HFpEF and obesity, a GLP-1 receptor agonist with demonstrated benefits for both glycemic management and reduction of HF-related symptoms is recommended.[29]

If HbA1c remains above target and the patient is taking either an SGLT2 inhibitor or a GLP-1 receptor agonist, then combined therapy with an SGLT2 inhibitor plus a GLP-1 receptor agonist may be considered, since this may provide additive reduction in the risk of adverse CV and kidney events.[29]​​​

The GLP-1 receptor agonists liraglutide, injectable semaglutide, and dulaglutide have the strongest evidence of CV risk reduction in patients with diabetes.[220]​​​​​[275][276][277][278]​​​[279]​ In addition to their beneficial effects on coronary artery disease (CAD), GLP-1 receptor agonists are the only drug class that has been shown to convincingly reduce nonfatal stroke.[216][218][280]​​​[281][282][283]​​ Unlike for SGLT2 inhibitors, the evidence for GLP-1 receptor agonists in reducing HF or improving CV outcomes in patients with HF has been inconsistent across trials.[285]​ Data from retrospective studies and meta-analyses have shown superiority of GLP-1 receptor agonists over other glucose-lowering drugs such as SGLT2 inhibitors and DPP-4 inhibitors in terms of peripheral arterial disease (PAD).[287]​ However, data from CV outcome trials regarding the impact of GLP-1 receptor agonists on PAD are scarce and further prospective studies are needed.​​​​

Semaglutide is the only GLP-1 receptor agonist that is available in both oral and injectable formulations. For information on oral semaglutide, see Emerging treatments.

The most common adverse effects of GLP-1 receptor agonists are gastrointestinal, particularly nausea, vomiting, and diarrhea; these are frequent but tend to reduce over time.[288] As these agents delay gastric emptying, patients may retain gastric contents despite standard preoperative fasting, increasing the risk of pulmonary aspiration during procedures involving general anesthesia or deep sedation. Anesthesiologists should perform an individualized assessment of aspiration risk, particularly in patients with diabetic gastroparesis, obesity, or GERD.[289]​ Patients should also be counseled about potential for ileus.[29]

An association with pancreatitis and pancreatic cancer has been reported in clinical trials, but causality has not been established; nonetheless, GLP-1 receptor agonists should be used with caution in patients with a history of pancreatitis.[29]​​[288]​ After a review of available data, the Food and Drug Administration (FDA) and European Medicines Agency (EMA) agreed that there was insufficient evidence to confirm an increased risk of pancreatic cancer with use of GLP-1-based therapies.[291] GLP-1 receptor agonists have also been associated with increased risk of gallbladder and biliary diseases including cholelithiasis and cholecystitis.[288]​​​​​

Hypoglycemia risk is increased when GLP-1 receptor agonists are used with sulfonylureas and insulin. Treatment deintensification of these agents or of diuretics, particularly in older and frail individuals, is recommended to avoid hypoglycemia and hypovolemia.[288] Diabetic ketoacidosis (DKA) has been reported in patients on a combination of a GLP-1 receptor agonist and insulin, when concomitant insulin was either rapidly reduced or discontinued; insulin reductions should therefore be undertaken in a cautious stepwise manner, with capillary blood glucose monitoring.[288]​​

In rodent studies, GLP-1 receptor agonists were associated with medullary thyroid cancer, resulting in a black box warning for these agents in patients with a personal or family history of multiple endocrine neoplasia type 2 or medullary thyroid cancer; however, there is conflicting evidence as to whether this risk applies in humans.[288][292][293][294][295]​​​​

The EMA and FDA are reviewing data on the risk of suicidal thoughts and thoughts of self-harm with GLP-1 receptor agonists, following reports of such occurrences in people using liraglutide and semaglutide.[296][297][298]​​​ Notably, real-world data from one US nationwide retrospective cohort study using electronic health records showed no increased risk of suicidal ideation with semaglutide compared with non-GLP-1 receptor agonist anti-obesity or antihyperglycemic drugs.[299] This aligns with a meta-analysis of 27 randomized-controlled trials, which also found no significant increase in suicide or self-harm events in adults with diabetes or obesity receiving GLP-1 receptor agonists versus placebo.[300]

The EMA has identified nonarteritic anterior ischemic optic neuropathy (NAION) as a very rare adverse effect of semaglutide, following evidence of a small increased risk in adults with type 2 diabetes. Patients should be advised to report sudden or worsening vision loss, and treatment should be discontinued if NAION is confirmed.[301] There is also some concern that GLP-1 receptor agonists, through their rapid glucose-lowering effects, may increase the risk of transient worsening of preexisting diabetic retinopathy.[302][303][304]​​ Further studies are required to elucidate this relationship.

The SGLT2 inhibitors empagliflozin, dapagliflozin, and canagliflozin have the strongest evidence of CV risk reduction in patients with diabetes.[121][220]​​​[242][243][244][245][246][247][248]​​ Only empagliflozin and canagliflozin have shown reduction in major adverse cardiac events (MACE) in patients with type 2 diabetes.[249]​ Ertugliflozin has shown benefit in reducing HF hospitalization, but not MACE.[252][253]​​​​

SGLT2 inhibitors have been shown to improve CV outcomes in patients with HF regardless of left ventricular ejection fraction and irrespective of type 2 diabetes status.[218][234][235]​​​​[236][237][238][239][240][241]​​​​​​​​​ Studies have shown their potential to significantly reverse cardiac remodeling in patients with HF.[257][258][259][260][261]​​​ Accordingly, the European Society of Cardiology (ESC) now recommends dapagliflozin or empagliflozin for all patients with type 2 diabetes and CKD to reduce risk of HF hospitalization or CV death, regardless of whether they have a pre-existing HF diagnosis.​[256]​​

SGLT2 inhibitors also reduce the risk of serious hyperkalemia in people with type 2 diabetes at high CV risk without increasing the risk of hypokalemia, allowing the titration of guideline-directed medical therapy in patients with HF.[263]

An initial decline in eGFR is commonly observed after initiating an SGLT2 inhibitor but this decline is not associated with subsequent risk of CV or kidney events.[264]​ Thus, SGLT2 inhibitors should not be interrupted or discontinued in response to an initial eGFR decline.

SGLT2 inhibitors are generally well-tolerated; however, some serious adverse reactions have been documented. Adverse effects include a higher rate of diabetic ketoacidosis (DKA), acute kidney injury, and fracture. The EMA warns of the potential increased risk of toe amputation.[265] Meanwhile, the FDA states that amputation risk, while increased with canagliflozin, is lower than previously described, particularly when appropriately monitored.[266] The FDA and UK Medicines and Healthcare products Regulatory Agency (MHRA) warn of cases of necrotizing fasciitis of the perineum (also known as Fournier gangrene) observed in post-marketing surveillance of SGLT2 inhibitors.[267][268]​​​​​ Thus, SGLT2 inhibitors should be avoided in patients with conditions that increase the risk for limb amputations, and in patients prone to urinary tract or genital infections.

Sotagliflozin is the first dual SGLT1/SGLT2 inhibitor.[269] It inhibits both renal SGLT2 (promoting significant excretion of glucose in the urine, in the same way as other already available SGLT2 selective inhibitors) and intestinal SGLT1 (delaying glucose absorption and therefore reducing postprandial glucose).[269]​ It has been approved in people with HF (both with and without diabetes) and in patients with type 2 diabetes who have CKD or high risk of/established ASCVD, to reduce the risk of hospitalization for HF.[29]​ It is not currently approved for glycemic management of type 1 or type 2 diabetes. One concern with expanded use of SGLT inhibition is the infrequent but serious risk of DKA, including the atypical presentation of euglycemic ketoacidosis.[29]​​​​

Of note, the studies that led to the approved indication of sotagliflozin for HF excluded individuals with type 1 diabetes or a history of DKA.[270][271]​ In clinical trials of sotagliflozin in people with type 1 diabetes, results showed improvements in HbA1c and body weight; however, its use was associated with an eightfold increase in DKA compared with placebo.[29]​​[272]​ The risks and benefits of SGLT inhibitors in people with type 1 diabetes continue to be evaluated, with guidelines and consensus statements providing direction on patient selection and precautions.[29]​​[273]​​​​

Primary options

empagliflozin: 10 mg orally once daily initially, increase according to response, maximum 25 mg/day

or

canagliflozin: 100 mg orally once daily initially, increase according to response, maximum 300 mg/day

or

dapagliflozin: 5 mg orally once daily initially, increase according to response, maximum 10 mg/day

or

sotagliflozin: 200 mg orally once daily initially, increase according to response, maximum 400 mg/day

-- AND / OR --

liraglutide: 0.6 mg subcutaneously once daily for 1 week, then increase to 1.2 mg once daily, adjust dose according to response, maximum 1.8 mg/day

or

semaglutide: 0.25 mg subcutaneously once weekly for 4 weeks, then increase to 0.5 mg once weekly for 4 weeks, adjust dose according to response, maximum 1 mg/week

or

dulaglutide: 0.75 mg subcutaneously once weekly, then increase to 1.5 mg once weekly, adjust dose according to response, maximum 4.5 mg/week

Plus – lifestyle and behavioral therapy

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diabetic cardiovascular disease: stable and/or after intervention
Plus – 

lifestyle and behavioral therapy

Treatment recommended for ALL patients in selected patient group

Therapeutic lifestyle interventions such as medical nutrition therapy and increased physical activity have been shown in large clinical trials to improve glycemic, lipid, and blood pressure control, and to improve insulin sensitivity and markers of inflammation. They are also effective in achieving sustained weight loss and improvements in fitness.[47][71][164][165][166]​​​[167]

There is no ideal amount of macronutrients that people with diabetes should consume, and studies suggest that such recommendations should be decided on an individual basis.[164][171]​​​​ The Mediterranean diet, Dietary Approaches to Stop Hypertension (DASH), vegetarian, and vegan diets have all been demonstrated to be effective for people with diabetes.[164][172][173][174][175]​​​​​ European guidelines recommend a Mediterranean or plant-based diet with high unsaturated fat content for lowering cardiovascular (CV) risk in people with diabetes.[6] One meta-analysis found that red meat consumption was associated with higher risk of cardiovascular disease (CVD) and diabetes, while another reported moderate certainty evidence that a shift from animal-based to plant-based foods is beneficially associated with cardiometabolic health and all-cause mortality.[176][177]​​​​

Reducing overall carbohydrate intake has demonstrated some evidence for improving glycemia and one study found that among people with type 2 diabetes, greater adherence to low-carbohydrate diet patterns was associated with significantly lower all-cause mortality.[178]​ While the American Diabetes Association (ADA) suggests that adults with diabetes may consider reducing their overall carbohydrate intake to improve glycemia, it cautions that the optimal level of restriction and its long-term impact on CVD are not yet fully understood.[29]

Both World Health Organization (WHO) and European guidelines emphasize that carbohydrate quality, rather than quantity, is key.[179][180]​​​ The concept of carbohydrate quality refers to the nature and composition of carbohydrates in a food or in the diet, including the proportion of sugars, how quickly polysaccharides are metabolized and release glucose into the body (i.e., digestibility), and the amount of dietary fiber. It is recommended that carbohydrate intake should come primarily from high-fiber foods, such as whole grains, vegetables, whole fruits, and pulses.[179][180]​​​​​ Diets high in naturally occurring fiber have been shown to be protective against cardiometabolic disease and premature mortality. When choosing high-fiber foods, focus should be on minimally processed and largely intact whole grains, rather than products with finely milled whole grains that may also have added sugars, sodium, and saturated fats.[179][180]​​​​ Fiber-enriched foods and fiber supplements can be considered when sufficient intake cannot be obtained from diet alone.[179]​​

There is some evidence to suggest that reducing intake of high-glycemic-index foods, and generally reducing glycemic load, could be beneficial for preventing CVD; however, WHO guidelines do not currently recommend this approach, citing inconsistent findings from observational studies and little to no improvement in cardiometabolic risk factors in randomized controlled trials of lower-glycemic-index or lower-glycemic-load diets.[180][181]​​​

Replacing saturated fats and trans-fats with unsaturated fats and carbohydrates from foods containing naturally occurring dietary fiber (such as whole grains, vegetables, fruits, and pulses) reduces low-density lipoprotein cholesterol and also benefits CVD risk.​[164][182][183]​​​ Saturated fat should comprise <10% of total energy intake and trans-fats <1%.[179][183]​​​ Dietary fats should mainly come from plant-based foods high in mono- and poly-unsaturated fats, such as nuts, seeds, and nonhydrogenated, nontropical vegetable oils (e.g., olive oil, rapeseed/canola oil, soybean oil, sunflower oil, linseed oil).​​[179]

People with diabetes who have overweight or obesity should be supported with evidence-based nutritional support to achieve and maintain weight loss.[179] European guidelines recommend that a variety of weight-loss diets can be used equally effectively for weight management with type 2 diabetes, provided they can be followed and meet recommendations for protein, fat, micronutrient, and fiber intake. However, neither extreme high-carbohydrate, nor very-low-carbohydrate ketogenic diets are recommended.[179]​ One systematic umbrella review of published meta-analyses of studies comparing hypoenergetic diets for weight management in people with type 2 diabetes did not find evidence for any particular weight-loss diet over others (e.g., low-carbohydrate, high-protein, low-glycemic index, Mediterranean, high-monounsaturated fatty acid or vegetarian diets).​[184]

Intermittent fasting or time-restricted eating as strategies for weight and glucose management have gained popularity.[185]​ They have been shown to result in mild to moderate weight loss (3% to 8% loss from baseline) over 8-12 weeks, with no significant difference in weight loss when compared with continuous calorie restriction.[29]​ The ADA advises that due to its simplicity, intermittent fasting may lend itself as a useful strategy for people with diabetes who are looking for practical eating management tools.[29]​​ People with diabetes who are on insulin and/or secretagogues should be medically monitored during the fasting period.[29]​​​

Evidence indicates that low- and very-low-energy diets (<3500 kJ/day [<840 kcal/day]), using total diet replacement formula diet products (replacing all meals) or partial liquid meal replacement products (replacing 1-2 meals per day) for the weight-loss phase, are most effective for weight loss and reduction of other cardiometabolic risk factors when compared with the results from self-administered food-based weight-loss diets.[179][186]​​ Low-energy nutritionally complete formula diets with a total diet replacement induction phase also appear to be the most effective dietary approach for achieving type 2 diabetes remission.[179]​ One population-based cohort study found that those who achieved remission from diabetes, even for a short time, had a much lower risk of CVD events, including MI and stroke, as well macrovascular and microvascular complications.[187]​​​

Physical activity: at least 150 minutes divided over ≥3 days per week of moderate- to vigorous-intensity aerobic physical activity with no more than 2 consecutive days without exercise.[6][29]​​ Shorter durations (minimum 75 minutes per week) of vigorous-intensity or interval training may be sufficient for more physically fit individuals.​[29]​ In the absence of contraindications, resistance training 2-3 times per week on nonconsecutive days is also recommended.[6][29]​​​​​ The ADA recommends interrupting sedentary activity every 30 minutes with short bouts of physical activity.​[29]​​ Older adults may benefit from flexibility and balance exercise 2-3 times per week.[29]​​

All patients with diabetes should be advised to quit smoking or not start.[29]​ Smoking counseling and other forms of smoking cessation therapy should be incorporated into routine diabetes care.[29]​ Varenicline combined with nicotine replacement therapy may be more effective than varenicline alone and the ADA recommends referring patients for combination treatment consisting of both tobacco/smoking cessation counseling and pharmacologic therapy.[29][191] The ADA does not support e-cigarettes as an alternative to smoking or to facilitate smoking cessation.[29]​ Patients who quit smoking are prone to weight gain; therefore, it is important to have weight management strategies in place to maximize the CV benefits of smoking cessation.[47]​​​​​ See Smoking cessation.​​​​​

Consider – weight management

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diabetic cardiovascular disease: stable and/or after intervention
Consider – 

weight management

Treatment recommended for SOME patients in selected patient group

Modest and sustained weight loss of at least 3% to 7% is recommended for most patients with type 2 diabetes who have overweight or obesity.[29] This degree of weight reduction significantly improves glycemia, blood pressure, and lipids and may reduce the need for disease-specific drugs.[29] Sustained loss of >10% of body weight usually confers greater benefits, including disease-modifying effects and possible remission of type 2 diabetes, and may improve long-term cardiovascular (CV) outcomes and mortality.[29]​ People with diabetes and overweight or obesity should be informed of the potential benefits of both modest and more substantial weight loss, and supported in exploring the full range of available treatment options.[29]

Obesity pharmacotherapy should be considered as an adjunct to lifestyle interventions and behavioral counseling to improve CV risk factors in people with type 2 diabetes who have overweight or obesity.[6][29]​​[169]​​​​​​​​ ​When choosing glucose-lowering drugs for this patient group, the American Diabetes Association (ADA) recommends that healthcare professionals should prioritize those with a beneficial effect on weight; this includes glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., semaglutide) and tirzepatide (a dual glucose-dependent insulinotropic polypeptide [GIP]/GLP-1 receptor agonist). Two phase 3 trials have demonstrated the potential for use of tirzepatide for obesity, with adverse effects similar to those seen with GLP-1 receptor agonists.[192][193]​​​​ If these drugs are not tolerated or contraindicated, other obesity treatment options may be considered, including phentermine, orlistat, phentermine/topiramate, or naltrexone/bupropion.[29]​​

​​Meanwhile, the European Society of Cardiology (ESC) recommends GLP-1 receptor agonists or sodium-glucose cotransporter-2 (SGLT2) inhibitors as the glucose-lowering agents of choice for weight loss in type 2 diabetes, in view of their proven CV benefits for these patients.[6][195]

When initiating chronic weight management treatment, if a patient achieves >5% weight loss after 3 months, continuing the drug long-term should be considered, unless factors like poor tolerability, financial cost, or individual preference suggest otherwise.[29] If <5% weight loss occurs after 3 months, the decision to continue treatment should carefully weigh the benefits against the glycemic response, other available treatment options, treatment tolerance, and overall treatment burden.[29]

Ongoing monitoring of weight management goals is recommended.[29] The ADA recommends that weight management pharmacotherapy should be continued beyond reaching weight loss goals to maintain the health benefits and avoid weight regain.[29] Sudden discontinuation of drugs like semaglutide and tirzepatide can lead to regaining up to two-thirds of the weight lost within one year.[196][197][198] Shared decision-making is crucial to determine the best long-term approach, which could include continuing the lowest effective dose, using intermittent therapy, or discontinuing the drug with close weight monitoring.[29]

For those not reaching goals, the ADA recommends evaluating weight management therapies and intensifying treatment with additional approaches (e.g., metabolic surgery, additional pharmacologic agents, and structured lifestyle management programs).[29]​​

As well as considering specific drugs to treat obesity, healthcare professionals should carefully review the individual’s concomitant drug treatments and, whenever possible, minimize or provide alternatives for drugs that promote weight gain. Examples of drugs associated with weight gain include antipsychotics (e.g., clozapine, olanzapine, risperidone), some antidepressants (e.g., tricyclic antidepressants, some selective serotonin-reuptake inhibitors, monoamine oxidase inhibitors), glucocorticoids, injectable progestins, some anticonvulsants (e.g., gabapentin, pregabalin), beta-blockers, and possibly sedating antihistamines and anticholinergics.[29]​​

A large number of studies have demonstrated that metabolic surgery achieves superior glycemic management and reduction of CV risk in people with type 2 diabetes and obesity compared with nonsurgical intervention.[9][199]​​​ It has also been shown to reduce microvascular complications, cancer risk, and all-cause mortality in people with obesity and type 2 diabetes.[29]​​​[200][201][202]​​​​​​​​​​​ Of note, one meta-analysis reported a 50% reduction in macrovascular complications following bariatric surgery in patients with type 2 diabetes and extreme obesity (BMI ≥40 kg/m²).[200]​ Another meta-analysis found that metabolic surgery reduced the risk of any CV event by 44% and yielded a risk reduction of over 55% in overall mortality and 69% in CV mortality in patients with type 2 diabetes.[203]

Vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) are the most commonly performed procedures. Both result in an anatomically smaller stomach pouch; in VSG, approximately 80% of the stomach is removed, leaving behind a long, thin sleeve-shaped pouch, whereas RYGB creates a much smaller stomach pouch (roughly the size of a walnut), which is then attached to the distal small intestine, thereby bypassing the duodenum and jejunum.[29]​​

The ADA recommends metabolic surgery to treat type 2 diabetes in adults with BMI ≥30 kg/m² (≥27.5 kg/m² for Asian-Americans) who are otherwise good surgical candidates.[29]​​​ The ESC recommends that bariatric surgery be considered for all patients with type 2 diabetes and BMI ≥35 kg/m² who have not achieved sufficient weight loss through lifestyle interventions and drug treatment.[6]​ Metabolic surgery is best done in a high-volume, specialized center to reduce the risk of perioperative and longer-term complications.[29]​​​

For more comprehensive information, see Obesity in adults.

Consider – antiplatelet therapy

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diabetic cardiovascular disease: stable and/or after intervention
Consider – 

antiplatelet therapy

Treatment recommended for SOME patients in selected patient group

Aspirin is recommended for secondary prevention in those with a history of atherosclerotic cardiovascular disease (ASCVD).[29]​ Clopidogrel (a P2Y12 inhibitor) is an alternative for patients with aspirin allergy or intolerance.[29]​​

In people with stable coronary and/or peripheral artery disease and low bleeding risk, the American Diabetes Association (ADA) and European Society of Cardiology (ESC) recommend combination treatment with aspirin and low-dose rivaroxaban (a direct oral anticoagulant [DOAC]) for secondary prevention.[29]​​​[336]​​ Rivaroxaban, when combined with aspirin, provides complementary antithrombotic effects and may also improve endothelial function.[337]

Following acute coronary syndrome (ACS), dual antiplatelet therapy with a combination of aspirin and a P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel) is indicated.[338]​​ Evidence supports use of either ticagrelor or clopidogrel if no PCI was performed, and clopidogrel, ticagrelor, or prasugrel if PCI was performed.[29]​​[339]​​​ Generally, prasugrel and ticagrelor have better efficacy in patients with diabetes and are preferred to clopidogrel for patients who undergo PCI.[336][339]​​​

Short-term dual antiplatelet therapy is also recommended after high-risk transient ischemic attack (TIA) and minor stroke.[340]

Extending dual antiplatelet therapy beyond 1 year may reduce long-term risk of recurrent atherosclerotic events.[336]​ However, recommendations regarding length of treatment are rapidly evolving and should be determined by an interprofessional team approach that includes a cardiologist following ACS or a neurologist following TIA/stroke.[29]​​ The benefits versus risk of bleeding and thrombosis should be evaluated based on the coronary anatomy and extent of CAD, PCI complexity, bleeding risk, age, and patient’s medical comorbidities such as anemia or renal failure.[341]

To reduce risk of gastrointestinal bleeding, proton-pump inhibitors are recommended for all patients on a combination of antiplatelet or anticoagulant therapy, and should be considered for those on a single agent depending on their individual bleeding risk, according to the ESC.[6]

Primary options

aspirin: 75-162 mg orally once daily

Secondary options

clopidogrel: 75 mg orally once daily

OR

aspirin: 75-162 mg orally once daily

and

rivaroxaban: 2.5 mg orally twice daily

OR

aspirin: 325 mg orally as a loading dose, followed by 75-162 mg once daily

-- AND --

ticagrelor: 180 mg orally as a loading dose, followed by 90 mg twice daily for 12 months, then 60 mg twice daily if treatment is required beyond 12 months

or

prasugrel: 60 mg orally as a loading dose, followed by 10 mg once daily

or

clopidogrel: 300 mg orally as a loading dose, followed by 75 mg once daily

Consider – guideline-directed management and therapy

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diabetic cardiovascular disease: stable and/or after intervention
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with heart failure
Consider – 

guideline-directed management and therapy

Treatment recommended for SOME patients in selected patient group

Patients with diabetes and heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF) should receive heart failure (HF) therapy as per current HF guidelines.[29]​​[153][255]

Presence of HF in patients with type 2 diabetes influences choice of antihyperglycemic agent. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are recommended in all patients with HF and type 2 diabetes, as they reduce risk of HF-related hospitalization and mortality.[29][256]​​ Thiazolidinediones (e.g., pioglitazone) and saxagliptin (a dipeptidyl peptidase-4 [DPP-4] inhibitor) have been associated with an increased risk of HF hospitalizations and are not recommended in patients with or at risk of HF.[29][153][255]​​​​ Metformin, insulin, and the DPP-4 inhibitors sitagliptin and linagliptin are considered neutral in terms of their effect on HF outcomes.[6]​ In patients with obesity and HFpEF, semaglutide (a GLP-1 receptor agonist) has been shown to reduce HF-related symptoms, improve exercise function, and result in greater weight loss compared with placebo.[366]​ In patients with symptomatic HFpEF and obesity, a GLP-1 receptor agonist with demonstrated benefits for both glycemic management and reduction of HF-related symptoms is therefore recommended.[29]

Screening for HF in patients with diabetes is important for starting therapy early and optimizing prognosis. The ADA recommends annual screening of asymptomatic adults with diabetes for HF.[29]​​

See Heart failure with reduced ejection fraction and Heart failure with preserved ejection fraction.

Consider – management of cardiovascular risk and kidney failure risk

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diabetic cardiovascular disease: stable and/or after intervention
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with chronic kidney disease
Consider – 

management of cardiovascular risk and kidney failure risk

Treatment recommended for SOME patients in selected patient group

Chronic kidney disease (CKD) is a risk factor for atherosclerotic cardiovascular disease (ASCVD), and declining kidney function (lower glomerular filtration rate [GFR], higher albuminuria) is associated with progressively increased risk of coronary disease.[80]​ Furthermore, CVD (in addition to diabetes) is a risk factor for CKD progression and eventual kidney failure requiring replacement therapy (dialysis or kidney transplant).[367]​ Reducing the risk of both cardiovascular (CV) and kidney adverse events is key in patients with type 2 diabetes, ASCVD, and comorbid CKD. Standard lifestyle and risk factor modifications, including blood pressure (BP), lipid, glycemic, and weight management, are important. Additionally, specific pharmacologic interventions are recommended.

Either a sodium-glucose cotransporter-2 (SGLT2) inhibitor or glucagon-like pepide-1 (GLP-1) receptor agonist with demonstrated benefit in this population should be used to improve glycemic control, slow CKD progression, and reduce CV events.[29]​ ​In advanced CKD (eGFR <30 mL/min/1.73 m²), a GLP-1 receptor agonist is preferred due to lower hypoglycemia risk and established CV benefit.[29] Combination therapy with a GLP-1 receptor agonist and SGLT2 inhibitor may be appropriate for some patients to provide additive risk reduction (e.g., if HbA1c remains above target while on one agent).[29]

The American Diabetes Association (ADA) strongly recommends an ACE inhibitor or angiotensin-II receptor antagonist for the treatment of hypertension in patients with diabetes and CKD - particularly those with albuminuria (urinary albumin-to-creatinine ratio ≥30 mg/g) - to reduce the risk of CKD progression and CV events.[29] Kidney Disease: Improving Global Outcomes (KDIGO) guidelines make the same recommendation, and also recommend considering one of these agents in patients with albuminuria and normal blood pressure.[368] European Society of Cardiology and American Heart Association/American College of Cardiology guidelines recommend the use of an ACE inhibitor or angiotensin-II receptor antagonist in all patients with chronic coronary disease and diabetes, even in the absence of hypertension, to reduce CV risk, particularly in those with HF or CKD.[6]​​​​​​[314]

For people with type 2 diabetes and CKD with albuminuria who are already on maximum tolerated ACE inhibitor or angiotensin-II receptor antagonist therapy, the addition of finerenone (a non-steroidal mineralocorticoid receptor antagonist) is recommended.[369][370]​​[6][29]​​​

Low-dose aspirin is recommended in patients with diabetes, CKD, and ASCVD to protect against further CV events.[6]

In patients with diabetes, CKD, and stable moderate or severe coronary artery disease (CAD), either an intensive medical strategy or an initial invasive strategy may be considered.[6]

Referral to a nephrologist should be considered.

See Diabetic kidney disease.

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