Management of Type 2 Diabetes
Start metformin immediately at diagnosis alongside lifestyle modifications for all patients with type 2 diabetes who have normal kidney function (eGFR ≥30 mL/min per 1.73 m²), and add an SGLT2 inhibitor as first-line dual therapy for those with eGFR ≥30 mL/min per 1.73 m². 1, 2
Initial Pharmacological Management
Metformin remains the cornerstone first-line medication for type 2 diabetes due to its proven mortality benefits, weight-neutral profile, low hypoglycemia risk, and low cost 1, 3. Start at 500 mg daily and increase by 500 mg every 1-2 weeks to a target dose of 2000 mg daily in divided doses 2, 4.
SGLT2 inhibitors should be initiated concurrently with metformin in patients with eGFR ≥30 mL/min per 1.73 m², as they provide substantial cardiovascular and kidney protection beyond glucose lowering 1, 2. This dual therapy approach is now considered standard first-line treatment rather than sequential add-on therapy 1.
When to Add Third-Line Agents
If HbA1c targets are not achieved after 3 months on metformin plus SGLT2 inhibitor, add a long-acting GLP-1 receptor agonist 1, 2. GLP-1 RAs reduce cardiovascular events by 12-26% and promote weight loss exceeding 5% in most patients 3, 2.
For patients who cannot tolerate metformin or SGLT2 inhibitors, alternative agents include DPP-4 inhibitors, thiazolidinediones, or sulfonylureas, selected based on cardiovascular risk profile, weight considerations, and hypoglycemia risk 1.
Glycemic Targets
Target HbA1c <7% for most patients 1, 2, 4. However, adjust targets based on specific patient factors:
- More stringent targets (6.0-6.5%): Short disease duration, long life expectancy, no significant cardiovascular disease, achievable without hypoglycemia 1
- Less stringent targets (7.5-8.0%): History of severe hypoglycemia, limited life expectancy, advanced complications, extensive comorbidities 1
Fasting and premeal glucose should be maintained <130 mg/dL and postprandial glucose <180 mg/dL 1.
Lifestyle Interventions
Physical Activity
Prescribe at least 150 minutes per week of moderate-intensity aerobic activity spread over at least 3 days with no more than 2 consecutive days without exercise 1, 2, 5. This reduces HbA1c by 0.4-1.0% 3.
Add resistance training at least twice weekly to improve insulin sensitivity 2, 5. Include flexibility and balance exercises, particularly for older adults 5.
Break up sedentary time with frequent activity breaks throughout the day, as prolonged sitting worsens glycemic control even in those meeting exercise guidelines 1, 5.
Nutrition
Implement a reduced-calorie diet targeting 500-750 kcal/day deficit (1,200-1,500 kcal/day for women; 1,500-1,800 kcal/day for men) 1. This approach produces HbA1c reductions of 0.3-2.0% 1.
Emphasize nutrient-dense carbohydrate sources: vegetables, fruits, legumes, whole grains, and dairy products 1, 2. Avoid sugar-sweetened beverages entirely, including fruit juices 1.
Limit sodium intake to <2 g/day (<5 g sodium chloride) 1, 2.
For patients with chronic kidney disease not on dialysis, maintain protein intake at 0.8 g/kg body weight/day 2.
Weight Management
Target at least 5% weight loss for overweight or obese patients, as this produces meaningful improvements in glycemic control, lipids, and blood pressure 1, 2. Weight loss of 7-10% provides additional benefits 1, 6.
Insulin Therapy
Approximately one-third of patients with type 2 diabetes require insulin during their lifetime 3. Consider insulin when:
- Patients present with severe hyperglycemia (glucose ≥250 mg/dL or HbA1c >9%) 4
- Oral agents and GLP-1 RAs fail to achieve glycemic targets 1
- Patients experience acute illness, infection, or surgery requiring temporary intensification 7, 8
Insulin can be added to oral medications or used as monotherapy depending on clinical circumstances 1, 9.
Monitoring
Check HbA1c every 3 months until targets are achieved, then at least twice yearly 2, 4. Intensify treatment if goals are not met 4.
Home glucose monitoring is most useful for patients taking insulin or medications causing hypoglycemia, those initiating or changing therapy, and during intercurrent illness 4, 9. Its utility is limited in stable patients on metformin monotherapy 9.
Cardiovascular and Kidney Protection
Comprehensive cardiovascular risk reduction is mandatory 2. This includes:
- Statin therapy for dyslipidemia 1
- ACE inhibitor or ARB for hypertension with albuminuria 2
- Aspirin for secondary prevention 1
The cardiovascular and kidney benefits of SGLT2 inhibitors and GLP-1 RAs extend beyond glucose lowering, with 18-39% risk reductions for heart failure and kidney disease progression 3.
Diabetes Self-Management Education
Provide diabetes self-management education and support (DSMES) at diagnosis, annually, with health status changes, and during care transitions 2. This education should be culturally appropriate and cover medication management, glucose monitoring, nutrition, physical activity, and recognition of hypo- and hyperglycemia 8, 2.
Special Considerations
Renal Impairment
Metformin can be used with eGFR ≥30 mL/min per 1.73 m² but requires dose adjustment or discontinuation with more severe impairment 1, 10. SGLT2 inhibitors are recommended for patients with eGFR ≥30 mL/min per 1.73 m² 1.
Hypoglycemia Risk
Metformin and SGLT2 inhibitors do not cause hypoglycemia when used alone 1, 10. Sulfonylureas, meglitinides, and insulin carry significant hypoglycemia risk, particularly in elderly, malnourished, or renally impaired patients 7, 8. Beta-blockers may mask hypoglycemia symptoms 7, 8.
Drug Interactions
Multiple medications can affect glucose control 7, 8. Corticosteroids, thiazide diuretics, phenothiazines, thyroid hormones, and estrogens may worsen hyperglycemia 7. NSAIDs, salicylates, sulfonamides, and beta-blockers may potentiate hypoglycemia 7.
Common Pitfalls
Avoid delaying SGLT2 inhibitor initiation in patients with normal kidney function—these agents should be started with metformin, not added later 1.
Do not use quality metrics like "percentage of patients with HbA1c <7%" as rigid targets, as this contradicts the principle of individualized care 1.
Recognize secondary failure (loss of glycemic control over time despite adherence) as disease progression requiring treatment intensification, not patient failure 1, 7.
Do not mix LEVEMIR (insulin detemir) with other insulin preparations, as this alters the action profile 8.