Management of Type 2 Diabetes Mellitus and Insulin Resistance
For newly diagnosed type 2 diabetes, start metformin immediately alongside comprehensive lifestyle modifications unless the patient presents with ketosis, diabetic ketoacidosis, random blood glucose ≥250 mg/dL, or HbA1c >8.5% (in which case insulin therapy is required first). 1
Understanding Type 2 Diabetes and Insulin Resistance
Type 2 diabetes is a metabolic disorder where your body doesn't make enough insulin AND the insulin produced doesn't work effectively (insulin resistance), leading to sugar accumulation in the blood 2. This represents a progressive disease involving both pancreatic β-cell dysfunction and reduced insulin sensitivity in muscle, adipose tissue, and liver 3, 4. Insulin resistance is essential to the development of the majority of type 2 diabetes cases, stemming from both genetic predisposition and environmental factors including obesity, physical inactivity, and diet 4.
Initial Assessment and Treatment Algorithm
When to Start Insulin Immediately
You must initiate insulin therapy first if ANY of the following are present: 1
- Ketosis or diabetic ketoacidosis
- Random blood glucose ≥250 mg/dL
- HbA1c ≥8.5% (some guidelines suggest >9%) 5, 6
- Unclear distinction between Type 1 and Type 2 diabetes
For these patients, start insulin at 0.5 units/kg/day with adjustments every 2-3 days based on blood glucose monitoring 6. Add metformin after ketoacidosis resolves while continuing subcutaneous insulin 6. Many patients can eventually be weaned off insulin and managed with metformin and lifestyle changes 5, 6.
First-Line Therapy for All Other Patients
Metformin is the preferred initial pharmacologic agent alongside lifestyle modifications 5, 1. Start at 500 mg daily, increase by 500 mg every 1-2 weeks, targeting an ideal dose of 2000 mg daily in divided doses 5, 1. Metformin is inexpensive, has long-established efficacy and safety, and may reduce cardiovascular events and death 5.
Common pitfall: Metformin can be continued in declining renal function down to GFR 30-45 mL/min with dose reduction 5. Don't discontinue prematurely.
Comprehensive Lifestyle Modifications to Reduce Insulin Resistance
Exercise Protocol (Critical for Reducing Insulin Resistance)
Adults should engage in at least 150 minutes per week of moderate-intensity aerobic activity, with daily exercise or at least not allowing more than 2 days between sessions to decrease insulin resistance 5, 1. Aerobic bouts should last at least 10 minutes, progressing to 30 minutes/day most days 5.
Add resistance training 2-3 sessions per week on nonconsecutive days 5. This provides additive glycemic benefit beyond aerobic exercise alone and can lower A1C significantly in older adults 5.
Break up sedentary periods (≥30 minutes) by standing, walking, or light activity 5. Avoiding extended sedentary time helps prevent type 2 diabetes and aids glycemic control 5.
Nutrition Strategies
Implement evidence-based nutrition focusing on: 1
- Mediterranean, DASH, or vegetarian/vegan diets
- Fiber-rich whole grains while avoiding refined carbohydrates
- Weight loss of at least 5% for overweight/obese patients
Meal sequencing matters: Consume low-density foods (vegetables, salads, soups) first, followed by protein, then starchy foods to improve glycemic and insulin responses 7.
Chrononutrition principles: Eat most calories and carbohydrates at lunch and early afternoon, avoid late evening dinner, and maintain consistent meal timing 7.
Treatment Intensification When Metformin Alone Is Insufficient
When monotherapy fails to achieve A1C targets over 3 months, add a second agent 5. For patients with cardiovascular disease, kidney disease, or high cardiovascular risk, prioritize adding SGLT-2 inhibitors or GLP-1 receptor agonists, which reduce atherosclerotic cardiovascular disease by 12-26%, heart failure by 18-25%, and kidney disease by 24-39% over 2-5 years 3.
Other combination options include: 5
- Sulfonylureas
- Thiazolidinediones (pioglitazone improves insulin sensitivity in muscle and adipose tissue, inhibits hepatic gluconeogenesis, and improves dysfunctional glucose homeostasis) 8
- DPP-4 inhibitors
- Basal insulin
High-potency GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists produce >5% weight loss in most individuals, with some exceeding 10% 3.
Monitoring Protocol
- Check HbA1c every 3 months until target is reached 6, 1
- Recommend finger-stick blood glucose monitoring for patients on insulin or medications with hypoglycemia risk 1
- Monitor for hypoglycemia in patients taking insulin or insulin secretagogues, especially with exercise 5
Special Exercise Considerations
For patients on insulin or insulin secretagogues: Ingest added carbohydrate if pre-exercise glucose <100 mg/dL to prevent hypoglycemia 5. Hypoglycemia can occur hours after exercise due to increased insulin sensitivity 5.
For patients with peripheral neuropathy: Wear proper footwear, examine feet daily, and restrict to non-weight-bearing activities if foot injury or open sore present 5. However, 150 minutes/week of moderate exercise improves outcomes in prediabetic neuropathy 5.
For patients with autonomic neuropathy: Requires more thorough evaluation before starting exercise due to increased risk of exercise-induced injury, decreased cardiac responsiveness, postural hypotension, and impaired thermoregulation 5.