Frequently Ordered Medications for Multimorbid Patients
Type 2 Diabetes Mellitus
Metformin is the mandatory first-line agent for all newly diagnosed Type 2 diabetes patients unless contraindications exist. 1 Start metformin immediately at diagnosis alongside lifestyle modifications, with typical dosing of 500-1000 mg twice daily or extended-release formulation once daily. 1
Cardioprotective Glucose-Lowering Agents
SGLT2 inhibitors (empagliflozin, canagliflozin, or dapagliflozin) are required additions for patients with established CVD, heart failure, or CKD regardless of HbA1c level. 1 These agents reduce cardiovascular events, heart failure hospitalization, and mortality. 1
GLP-1 receptor agonists (liraglutide, semaglutide, or dulaglutide) are recommended for patients with CVD or very high cardiovascular risk to reduce cardiovascular events and mortality. 1 Liraglutide specifically reduces death risk in high-risk patients. 1
For patients with both diabetes and heart failure with reduced ejection fraction, SGLT2 inhibitors take priority over GLP-1 receptor agonists. 1
Glycemic Monitoring
- Monitor vitamin B12 levels periodically in metformin-treated patients, especially those with anemia or peripheral neuropathy, as long-term use causes biochemical B12 deficiency. 1
Hypertension
For diabetic patients with hypertension, initiate combination therapy with an ACE inhibitor or ARB plus either a calcium channel blocker or thiazide-like diuretic. 1 Target blood pressure is <130/80 mmHg for all diabetic patients. 1
First-Line Antihypertensive Classes
ACE inhibitors or ARBs are mandatory first-line therapy for diabetic patients with hypertension, coronary artery disease, or albuminuria (UACR ≥30 mg/g). 1, 2 These agents provide renoprotection beyond blood pressure reduction alone. 2
Thiazide-like diuretics (chlorthalidone or indapamide preferred over hydrochlorothiazide) should be combined with ACE inhibitors/ARBs as initial dual therapy. 1, 3 Long-acting agents like chlorthalidone reduce cardiovascular events more effectively. 1
Dihydropyridine calcium channel blockers (amlodipine 5-10 mg or nifedipine extended-release 30-60 mg daily) are the third component when triple therapy is needed. 1, 4, 3
Critical Monitoring
Monitor serum creatinine and potassium within 7-14 days after initiating ACE inhibitors, ARBs, or diuretics, then every 3 months if stable. 1
Never combine ACE inhibitors with ARBs—this increases adverse effects (hyperkalemia, acute kidney injury) without additional benefit. 1, 3, 2
Special Populations
- For fertile women of childbearing potential, calcium channel blockers (amlodipine or nifedipine) are the mandatory first-line choice because ACE inhibitors and ARBs cause fetal damage and are absolutely contraindicated in pregnancy. 4 Methyldopa or labetalol are acceptable alternatives. 4
Congestive Heart Failure
For diabetic patients with heart failure with reduced ejection fraction (HFrEF), the medication regimen must include an SGLT2 inhibitor, ACE inhibitor (or sacubitril/valsartan), beta-blocker, and mineralocorticoid receptor antagonist. 1
Core Heart Failure Medications
Sacubitril/valsartan is recommended instead of ACE inhibitors in HFrEF patients with diabetes who remain symptomatic despite treatment with ACE inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. 1
Beta-blockers are indicated for all patients with prior MI, active angina, or HFrEF. 1 Continue beta-blockers even in patients with COPD if bronchospasm is not present. 5
Mineralocorticoid receptor antagonists (spironolactone or eplerenone) should be added for resistant hypertension or symptomatic heart failure when patients are already on ACE inhibitors/ARBs and diuretics. 1 Monitor potassium closely when combining with ACE inhibitors/ARBs. 1
Medications to Avoid
Saxagliptin (DPP-4 inhibitor) is contraindicated in patients with high risk of heart failure. 1
Thiazolidinediones (pioglitazone and rosiglitazone) are contraindicated in heart failure as they worsen fluid retention. 1
Loop diuretics should be used cautiously in patients with concurrent COPD and right ventricular failure. 5
Hypercholesterolemia
High-intensity statins are mandatory first-line therapy for all diabetic patients over age 40 with any cardiovascular risk factors. 1 The primary goal is LDL-C <1.8 mmol/L (70 mg/dL) for very high-risk patients or <2.6 mmol/L (100 mg/dL) for high-risk patients. 1
Statin Therapy
Moderate-to-high intensity statins (atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily) should be initiated at diabetes diagnosis for patients over 40 years. 1 Aim for at least 30-40% LDL-C reduction. 1
For patients not reaching LDL-C targets on maximum tolerated statin doses, add ezetimibe 10 mg daily. 1
PCSK9 inhibitors (evolocumab or alirocumab) are recommended for very high-risk patients with persistent elevated LDL-C despite maximum tolerated statin plus ezetimibe, or for statin-intolerant patients. 1
Triglyceride Management
For fasting triglycerides ≥5.7 mmol/L (500 mg/dL), initiate triglyceride-lowering drugs (fibrates or omega-3 fatty acids) immediately to prevent acute pancreatitis. 1
Intensify lifestyle therapy and optimize glycemic control for triglycerides ≥1.7 mmol/L (150 mg/dL) or low HDL-C. 1
Chronic Obstructive Pulmonary Disease
Long-acting bronchodilators (LABA/LAMA combinations) are first-line maintenance therapy for symptomatic COPD patients. Standard combinations include tiotropium/olodaterol or umeclidinium/vilanterol.
Bronchodilator Therapy
Long-acting muscarinic antagonists (LAMA) such as tiotropium 18 mcg daily via inhaler provide 24-hour bronchodilation.
Long-acting beta-agonists (LABA) such as salmeterol or formoterol combined with LAMA provide superior symptom control compared to monotherapy.
Inhaled Corticosteroids
- Add inhaled corticosteroids (fluticasone, budesonide) to LABA/LAMA combinations only for patients with frequent exacerbations (≥2 per year) or blood eosinophil count ≥300 cells/μL.
COPD-Heart Failure Interactions
Beta-blockers may be given to COPD patients with left ventricular failure if bronchospasm is not present. 5 Cardioselective beta-blockers (metoprolol, bisoprolol) are preferred.
ACE inhibitors should be used to treat left ventricular failure in COPD patients. 5
Avoid digitalis in patients with right ventricular failure due to COPD. 5
Antiplatelet Therapy
Low-dose aspirin (75-100 mg daily) with a proton pump inhibitor is recommended for diabetic patients with established CVD or very high cardiovascular risk. 1
Proton pump inhibitor co-prescription is mandatory in patients receiving aspirin who are at high risk of gastrointestinal bleeding. 1
Low-dose rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily may be considered in diabetic patients with symptomatic lower extremity arterial disease. 1
Dual antiplatelet therapy (DAPT) prolongation beyond 12 months should be considered for up to 3 years in very high-risk diabetic patients who tolerate DAPT without major bleeding. 1
Critical Medication Interactions and Contraindications
NSAIDs are absolutely contraindicated in patients with heart failure as they worsen fluid retention and increase cardiovascular events. 5 Use acetaminophen, tramadol, or opioids for pain management instead. 5
Statins are contraindicated in women of childbearing potential not using reliable contraception. 1
Monitor for hypoglycemia when combining insulin or sulfonylureas with SGLT2 inhibitors or GLP-1 receptor agonists—dose reductions of insulin/sulfonylureas are typically required. 1