What is the management plan for an adult patient with type 2 diabetes mellitus (DM)?

Management of Type 2 Diabetes Mellitus in Adults

Start metformin immediately at diagnosis alongside comprehensive lifestyle modifications, then add a GLP-1 receptor agonist (preferably tirzepatide) or SGLT2 inhibitor at 3 months if HbA1c remains above 7%, with the choice determined by presence of heart failure, chronic kidney disease, or need for substantial weight loss. 1, 2, 3

Foundation: Universal Starting Point

Lifestyle Modifications (Mandatory for All Patients)

• Begin 1500 kcal/day caloric restriction with fat limited to 30-35% of total energy intake 3, 4
• Prescribe exactly 150 minutes weekly of moderate-intensity aerobic exercise spread over at least 3 days, with no more than 2 consecutive days without activity 2
• Add resistance training 2-3 sessions weekly on nonconsecutive days 2, 4
• Target minimum 5% body weight reduction for all overweight/obese patients before or concurrent with pharmacotherapy 2
• Provide diabetes self-management education and medical nutrition therapy by a registered dietitian at diagnosis, as this reduces A1C by 0.3-2% and lowers mortality risk 2

First-Line Pharmacotherapy

• Start metformin immediately at diagnosis (unless contraindicated) and continue it indefinitely as the foundation of treatment 1, 2, 3, 4, 5
• Monitor for vitamin B12 deficiency during long-term metformin use, especially if anemia or peripheral neuropathy develops 2, 4
• Target HbA1c between 7-8% for most adults 3, 4

Second-Line Therapy Algorithm (Add at 3 Months if HbA1c >7%)

For Patients WITH Cardiovascular/Renal Comorbidities

Immediately add SGLT2 inhibitor or GLP-1 receptor agonist alongside metformin at diagnosis (do not wait 3 months) based on the following hierarchy: 1, 2, 4

Choose SGLT2 Inhibitor When:

• Heart failure is present (either reduced or preserved ejection fraction) for glycemic management and prevention of heart failure hospitalizations 1
• Chronic kidney disease with eGFR 20-60 mL/min per 1.73 m² and/or albuminuria to minimize CKD progression, reduce cardiovascular events, and reduce heart failure hospitalizations 1, 4
• Note: Glycemic benefits of SGLT2 inhibitors are reduced at eGFR <45 mL/min per 1.73 m² 1

Choose GLP-1 Receptor Agonist When:

• Advanced CKD with eGFR <30 mL/min per 1.73 m² due to lower hypoglycemia risk and cardiovascular event reduction 1, 4
• Increased stroke risk or when all-cause mortality reduction is the primary goal 4

For Patients WITHOUT Cardiovascular/Renal Comorbidities

Add tirzepatide (dual GIP/GLP-1 receptor agonist) as the preferred second agent after 3 months of metformin plus lifestyle modifications if HbA1c remains >7% 1, 3

• Tirzepatide produces mean weight loss of 8.47 kg, with up to 67% of patients achieving ≥10% weight reduction and demonstrates superior glycemic control compared to standard GLP-1 receptor agonists 3
• Consider standard GLP-1 receptor agonists as alternatives, though they provide less weight loss and glycemic reduction than tirzepatide 3
• GLP-1 receptor agonists are preferred over insulin for glycemic management 1

Cost-Constrained Alternative Pathway

When newer agents are unaffordable, maximize glipizide dose 3, 4

• If HbA1c remains >8% after maximizing glipizide, add basal insulin 3, 4
• Immediately reduce glipizide dose by 50% when adding insulin to prevent severe hypoglycemia 3, 4
• Discontinue sulfonylureas once SGLT2 inhibitors or GLP-1 agonists achieve glycemic control, as they increase hypoglycemia risk without mortality benefit 4

Insulin Initiation Criteria

Initiate insulin immediately regardless of background therapy if any of the following are present: 1

• Evidence of ongoing catabolism (unexpected weight loss) 1
• Symptoms of hyperglycemia 1
• HbA1c >10% (>86 mmol/mol) or blood glucose ≥300 mg/dL (≥16.7 mmol/L) 1
• If insulin is used, combine with a GLP-1 receptor agonist for greater glycemic effectiveness and beneficial effects on weight and hypoglycemia 1

Monitoring Schedule

• Reassess medication plan and medication-taking behavior every 3-6 months and adjust as needed 1, 4
• If HbA1c falls below 6.5%, deintensify treatment immediately to avoid hypoglycemia and overtreatment 3, 4

Cardiovascular Risk Management

• Initiate at least moderate-intensity statin therapy for most patients aged 40 years or older to reduce cardiovascular mortality 2
• Target blood pressure <140/90 mm Hg 2
• Initiate ACE inhibitor or ARB (but not both) as first-line antihypertensive for renal protection 2

Screening for Complications

• Annual comprehensive dilated eye examination by ophthalmologist or optometrist starting immediately at diagnosis 2
• Annual comprehensive foot examination including visual inspection for skin integrity, callous formation, deformities, or ulcers 2
• Annual laboratory monitoring: lipid profile, spot urinary albumin-to-creatinine ratio, serum creatinine and eGFR, liver function tests, thyroid-stimulating hormone, vitamin B12 levels, and serum potassium 2

Critical Pitfalls to Avoid

• Never delay adding SGLT2 inhibitor or GLP-1 receptor agonist in patients with established cardiovascular disease, heart failure, or chronic kidney disease—add these immediately at diagnosis alongside metformin 1, 2, 4
• Never delay treatment intensification when patients fail to meet glycemic targets after 3 months, as therapeutic inertia worsens long-term outcomes 3, 4
• Never combine tirzepatide with DPP-4 inhibitors, as this provides no additional glucose lowering beyond tirzepatide alone 3
• Never continue sulfonylureas once SGLT2 inhibitors or GLP-1 agonists achieve glycemic control 4
• Never neglect ongoing lifestyle modifications throughout the entire treatment course regardless of medication regimen 2
• Never target HbA1c below 6.5%—this requires immediate deintensification 3, 4
• Never use DPP-4 inhibitors as they lack mortality benefit 4

Shared Decision-Making Framework

Use a person-centered approach considering: 1

• Effects on cardiovascular and renal comorbidities 1
• Hypoglycemia risk 1
• Impact on weight 1
• Cost and access 1
• Risk for adverse reactions and tolerability 1
• Individual preferences 1