How to Start Diabetic Medications in Adults with Type 2 Diabetes
At the time of type 2 diabetes diagnosis, initiate metformin therapy along with lifestyle interventions, unless metformin is contraindicated. 1
Step 1: Confirm the Diagnosis
Diagnose type 2 diabetes using any one of the following criteria (confirm with repeat testing on a subsequent day unless symptoms are present): 2
Check estimated glomerular filtration rate (eGFR) before starting metformin; metformin is contraindicated when eGFR < 30 mL/min/1.73 m². 1, 3
Step 2: Assess for Acute Complications Requiring Immediate Insulin
Start insulin immediately (with or without additional agents) if any of the following are present: 1, 3
- Diabetic ketoacidosis (DKA) or ketosis 1
- Random blood glucose ≥ 250 mg/dL 1
- HbA1c ≥ 9% (some guidelines use ≥ 8.5% in children) 1, 3
- Markedly symptomatic hyperglycemia (polyuria, polydipsia, nocturia, unintended weight loss) 1
If insulin is required:
- Begin basal insulin (NPH or long-acting analog) at 10 units once daily at bedtime or 0.1–0.2 units/kg body weight. 1, 3
- Titrate by 2–4 units every 3 days until fasting glucose is 80–130 mg/dL without hypoglycemia. 1, 3
- Continue metformin when insulin is added (unless contraindicated) because it reduces insulin requirements, provides cardiovascular benefit, and carries minimal hypoglycemia risk. 1, 3
Step 3: First-Line Therapy for Metabolically Stable Patients
For patients without acute complications (HbA1c < 9%, asymptomatic, no ketosis):
Metformin Initiation
- Start metformin 500 mg once or twice daily with meals. 1, 3
- Increase by 500 mg weekly to a target of 2000 mg daily (1000 mg twice daily) for maximal glucose-lowering effect. 1, 3
- Doses above 2000 mg add minimal benefit and increase gastrointestinal intolerance. 3
Lifestyle Interventions (Concurrent with Metformin)
- Prescribe individualized medical nutrition therapy by a registered dietitian. 1
- Target 5–7% weight loss through caloric restriction for overweight/obese patients. 1, 3
- Recommend ≥ 150 minutes/week of moderate-intensity aerobic activity plus resistance training 2–3 days/week. 1
- Limit non-academic screen time to < 2 hours daily. 1
Step 4: Check for Metformin Contraindications
Do not start metformin if: 1, 3
Dose adjustment required:
- When eGFR is 30–45 mL/min/1.73 m², reduce metformin dose by approximately 50%. 3
- When eGFR is 45–59 mL/min/1.73 m², monitor renal function every 3–6 months. 3
Step 5: Add Agents with Cardiovascular or Renal Benefit
For patients with established atherosclerotic cardiovascular disease (ASCVD), heart failure, or chronic kidney disease, add one of the following to metformin at diagnosis (independent of baseline HbA1c): 3, 4, 5, 6
GLP-1 Receptor Agonist (Preferred for ASCVD)
- Semaglutide, liraglutide, or dulaglutide provide 0.6–0.8% HbA1c reduction, 2–5 kg weight loss, and proven cardiovascular mortality benefit. 3, 4
- Minimal hypoglycemia risk when not combined with sulfonylureas. 3
- Start with low doses and titrate weekly or monthly per product labeling. 3
SGLT2 Inhibitor (Preferred for Heart Failure or CKD)
- Empagliflozin, dapagliflozin, or canagliflozin provide cardiovascular and renal protection independent of glucose lowering. 3, 4, 5, 6
- Lower HbA1c by 0.5–0.8% and promote weight loss without increasing hypoglycemia risk. 3
- Require eGFR > 20 mL/min/1.73 m² for continuation (initiation typically requires eGFR > 45 mL/min/1.73 m²). 3
- Educate patients to stop the drug and seek care if nausea, vomiting, or abdominal pain develop (euglycemic DKA risk). 3
Step 6: Set Glycemic Targets
Standard target for most adults: HbA1c < 7% 1, 3
More stringent target (< 6.5%) may be appropriate for: 1, 3
- Short diabetes duration
- Long life expectancy
- No significant cardiovascular disease
- Low hypoglycemia risk
Less stringent target (7.5–8%) is appropriate for: 1, 3
- History of severe hypoglycemia
- Limited life expectancy (< 10 years)
- Advanced microvascular or macrovascular complications
- Extensive comorbidities
- Long-standing diabetes difficult to control despite multiple agents
Step 7: Monitor and Intensify Therapy
Reassess HbA1c at 3 months after starting or changing therapy. 1, 3
If HbA1c remains > 7% after 3–6 months of metformin monotherapy at maximal tolerated dose, add a second agent: 1, 3
- GLP-1 receptor agonist (preferred for additional cardiovascular benefit) 3
- SGLT2 inhibitor (preferred for heart failure or CKD) 3
- Basal insulin (if other agents are contraindicated or not tolerated) 1, 3
- DPP-4 inhibitor (if GLP-1 RA and SGLT2i are not options; provides 0.5–0.8% HbA1c reduction without cardiovascular benefit) 3
Perform HbA1c testing quarterly in patients whose therapy has changed or who are not meeting goals. 1
Perform HbA1c testing at least twice yearly in patients meeting treatment goals with stable glycemic control. 1
Step 8: Provide Diabetes Self-Management Education
- All patients should receive diabetes self-management education (DSME) at diagnosis and as needed thereafter. 1
- DSME should address psychosocial issues because emotional well-being is associated with positive diabetes outcomes. 1
Common Pitfalls to Avoid
- Do not delay metformin initiation while waiting for lifestyle changes alone to work; start metformin at diagnosis. 1
- Do not discontinue metformin when adding insulin or other agents unless contraindicated; it remains foundational therapy throughout intensification. 1, 3
- Avoid therapeutic inertia: intensify therapy within 3 months if HbA1c remains above target. 3
- Do not use sulfonylureas as first-line therapy in older adults or those with renal impairment; they markedly increase hypoglycemia risk and lack cardiovascular benefit. 3, 7
- Do not combine GLP-1 receptor agonists with DPP-4 inhibitors; no additional glucose-lowering benefit is observed. 3
- Monitor vitamin B12 levels periodically in patients on long-term metformin, especially if anemia or peripheral neuropathy develop. 1, 3