Initial Treatment for Diabetes
Start metformin immediately at diagnosis for type 2 diabetes alongside lifestyle modifications, unless the patient presents with severe hyperglycemia (A1C ≥8.5% or glucose ≥250 mg/dL), ketosis, or ketoacidosis—in which case insulin must be initiated first. 1
Type 2 Diabetes: Initial Management Algorithm
Step 1: Assess Disease Severity at Presentation
Metabolically stable patients (A1C <8.5%, asymptomatic):
- Begin metformin as first-line pharmacologic therapy if renal function is normal 2, 1
- Start at 500 mg daily, increase by 500 mg every 1-2 weeks up to maximum 2,000 mg daily in divided doses 1
- Metformin reduces cardiovascular events and mortality while being cost-effective with extensive safety data 1
Moderate hyperglycemia (A1C ≥8.5% without acidosis):
- Initiate basal insulin plus metformin simultaneously 2
- Use basal insulin at 0.5 units/kg while titrating metformin to therapeutic dose 2
- This dual approach achieves glycemic control more rapidly in symptomatic patients with polyuria, polydipsia, or weight loss 2
Severe hyperglycemia with ketosis/ketoacidosis:
- Start insulin therapy immediately (subcutaneous or intravenous depending on acidosis severity) 2
- Once acidosis resolves, add metformin while continuing subcutaneous insulin 2
- For blood glucose ≥600 mg/dL, evaluate for hyperglycemic hyperosmolar nonketotic syndrome 2
Step 2: Implement Comprehensive Lifestyle Interventions
Physical activity prescription:
- At least 150 minutes of moderate-intensity aerobic activity weekly plus resistance training at least twice per week 1, 3
- Reduce sedentary time throughout the day 1
- Physical activity alone can reduce A1C by 0.4-1.0% 3
Nutrition therapy:
- Focus on nutrient-dense, high-quality foods while decreasing calorie-dense, nutrient-poor foods 2, 1
- Eliminate or minimize sugar-added beverages 2
- Target 5-10% weight loss from baseline, which produces meaningful metabolic improvements 1, 3
- Individualized medical nutrition therapy preferably delivered by a registered dietitian 1
Step 3: Set Glycemic Targets
A1C goal <7% for most adults with type 2 diabetes 2, 1
- More stringent targets (<6.5%) appropriate for selected patients who can achieve this without significant hypoglycemia, particularly those on metformin monotherapy with short disease duration 2
- Less stringent targets (7.5%) may be appropriate if hypoglycemia risk is elevated 2
Monitor A1C every 3 months until target achieved, then at least twice yearly 2, 1
Step 4: Treatment Intensification When Needed
If metformin monotherapy fails to achieve A1C target after 3 months:
- Add a second agent from: GLP-1 receptor agonists, SGLT-2 inhibitors, DPP-4 inhibitors, sulfonylureas, thiazolidinediones, or basal insulin 1, 3
- Prioritize GLP-1 receptor agonists or SGLT-2 inhibitors in patients with established cardiovascular disease, heart failure, kidney disease, or high cardiovascular risk 3
- These agents reduce atherosclerotic cardiovascular disease by 12-26%, heart failure by 18-25%, and kidney disease progression by 24-39% over 2-5 years 3
- High-potency GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists produce >5% weight loss in most patients, often exceeding 10% 3
For patients initially on insulin plus metformin who achieve glycemic targets:
- Taper insulin over 2-6 weeks by decreasing dose 10-30% every few days 2
- Continue metformin maintenance therapy 2
Type 1 Diabetes: Initial Management
All patients with type 1 diabetes require insulin therapy from diagnosis 1
Recommended starting approach:
- Approximately one-third of total daily insulin as basal insulin (such as insulin glargine once daily) 2, 4
- Remaining two-thirds as short-acting premeal insulin 2
- Most patients should use multiple daily injections (≥3 injections daily) or continuous subcutaneous insulin infusion 1
- Intensive insulin therapy clearly reduces microvascular complications and cardiovascular disease risk 1
Insulin glargine administration specifics:
- Administer subcutaneously once daily at the same time each day (any time, but consistent) 4
- Rotate injection sites within the same region (abdomen, thigh, or deltoid) to prevent lipodystrophy 4
- Never dilute, mix with other insulins, or administer intravenously 4
- Visually inspect for particulate matter; use only if clear and colorless 4
Special Populations: Children and Adolescents
Youth with type 2 diabetes require immediate pharmacologic therapy at diagnosis alongside lifestyle counseling 2
Treatment algorithm for pediatric type 2 diabetes:
- A1C <8.5% without ketosis: Start metformin, titrate to 2,000 mg daily as tolerated 2
- A1C ≥8.5% without acidosis: Start metformin plus basal insulin at 0.5 units/kg 2
- Ketosis/ketoacidosis present: IV or subcutaneous insulin until acidosis resolves, then add metformin 2
For youth ≥10 years old failing metformin therapy:
- Consider adding liraglutide (GLP-1 receptor agonist) if no personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 2
Lifestyle recommendations for youth:
- At least 60 minutes of moderate-to-vigorous physical activity daily with muscle/bone strengthening ≥3 days weekly 2
- Family-centered, culturally appropriate nutrition counseling 2
Critical Implementation Considerations
Common pitfalls to avoid:
- Never delay metformin initiation in stable type 2 diabetes—pharmacologic therapy should begin at diagnosis, not after failed lifestyle modification 2, 1
- Do not use insulin as first-line therapy in stable type 2 diabetes; reserve for severe hyperglycemia, ketosis, or metformin failure 2
- Avoid injecting insulin into areas of lipodystrophy, which causes erratic absorption and hyperglycemia 4
- When switching injection sites from lipodystrophic to normal areas, monitor closely for hypoglycemia 4
Monitoring requirements:
- Increase blood glucose monitoring frequency during any insulin regimen changes 4
- For patients on ACE inhibitors, ARBs, or diuretics with metformin, monitor serum creatinine/eGFR and potassium at least annually 5
- Self-monitoring of blood glucose should be individualized based on pharmacologic regimen 2