What are the steps in managing type 2 diabetes mellitus in an adult patient?

Managing Type 2 Diabetes Mellitus in Adults

Initial Management: Universal Starting Point

All adults with type 2 diabetes must begin metformin immediately (unless contraindicated) combined with comprehensive lifestyle modifications at diagnosis, as this combination reduces mortality and provides the foundation for all subsequent therapy. 1, 2, 3

Lifestyle Modifications (Mandatory for All Patients)

• Caloric restriction: Limit intake to 1500 kcal/day 2, 4, 3
• Fat restriction: Limit dietary fat to 30-35% of total energy intake 2, 4, 3
• Aerobic exercise: Prescribe 150 minutes per week of moderate-intensity aerobic activity, spread over at least 3 days with no more than 2 consecutive days without activity 1, 2, 3
• Resistance training: Perform 2-3 sessions per week on nonconsecutive days, involving large muscle groups 1, 2, 3
• Weight loss target: Achieve minimum 5% body weight reduction for all overweight/obese patients 3
• Reduce sedentary time: Break up periods of sitting (≥30 minutes) by standing, walking, or performing light physical activity 1

Metformin Initiation and Monitoring

• Start metformin at diagnosis unless contraindicated, continuing it long-term as the foundation of treatment 2, 3, 5
• Monitor for vitamin B12 deficiency during long-term use, especially if anemia or peripheral neuropathy develops 2, 3
• Expected glycemic benefit: Metformin reduces HbA1c by approximately 1.4% and fasting plasma glucose by 53 mg/dL 5

Glycemic Targets and Monitoring Schedule

• Target HbA1c: 7-8% for most adults with type 2 diabetes 2, 4, 3
• Deintensify treatment immediately if HbA1c falls below 6.5% to avoid hypoglycemia and overtreatment 2, 4
• Reassess medication plan every 3-6 months and adjust based on glycemic control, weight goals, metabolic comorbidities, and hypoglycemia risk 1, 2, 3

Second-Line Therapy Algorithm: When to Add Agents

If HbA1c remains above 7-8% after 3 months of metformin plus lifestyle modifications, add a second agent based on the following comorbidity-driven algorithm:

Patients WITH Cardiovascular or Renal Comorbidities

Add SGLT2 inhibitor or GLP-1 receptor agonist immediately alongside metformin at diagnosis if any of the following are present: 1, 2, 3

Choose SGLT2 Inhibitor When:

• Heart failure present (either reduced or preserved ejection fraction) for glycemic management and prevention of heart failure hospitalizations 1, 2, 3
• Chronic kidney disease with eGFR 20-60 mL/min/1.73 m² and/or albuminuria to minimize CKD progression, reduce cardiovascular events, and reduce heart failure hospitalizations 1, 2, 3
• Note: Glycemic benefits of SGLT2 inhibitors are reduced at eGFR <45 mL/min/1.73 m² 1

Choose GLP-1 Receptor Agonist When:

• Advanced CKD with eGFR <30 mL/min/1.73 m² (preferred over SGLT2 inhibitor) due to lower hypoglycemia risk and cardiovascular event reduction 1, 2, 3
• Increased stroke risk or when all-cause mortality reduction is the primary goal 2
• Substantial weight loss needed 2

Patients WITHOUT Cardiovascular or Renal Comorbidities

Select pharmacologic agents that address both individualized glycemic and weight goals: 1

For Patients with BMI >25:

• Add tirzepatide (dual GIP/GLP-1 RA) as the preferred second agent after metformin, as it provides superior glycemic control and substantial weight loss (mean 8.47 kg, with up to 67% achieving ≥10% weight reduction) compared to all other options 1, 4
• Alternative: Standard GLP-1 receptor agonists, though they provide less weight loss and glycemic reduction than tirzepatide 4

For Patients with Normal BMI:

• Consider early combination therapy at treatment initiation to shorten time to attainment of individualized treatment goals 1
• GLP-1 receptor agonist is preferred to insulin for greater glycemic effectiveness and beneficial effects on weight 1

Cost-Constrained Situations

When newer agents (SGLT2 inhibitors, GLP-1 agonists) are unaffordable:

• Maximize glipizide dose as an alternative 2
• If HbA1c remains >8% after maximizing glipizide, add basal insulin 2
• Immediately reduce glipizide dose by 50% when adding insulin to prevent severe hypoglycemia 2, 4

Insulin Initiation Criteria

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

• Evidence of ongoing catabolism (unexpected weight loss)
• Symptoms of hyperglycemia present
• HbA1c >10% (>86 mmol/mol)
• Blood glucose ≥300 mg/dL (≥16.7 mmol/L)

If insulin is used, combine with a GLP-1 receptor agonist (including dual GIP/GLP-1 RA) for greater glycemic effectiveness and beneficial effects on weight and hypoglycemia 1

Hypoglycemia Prevention and Management

• In patients taking insulin or insulin secretagogues: Physical activity may cause hypoglycemia if medication dose or carbohydrate consumption is not altered 1
• Pre-exercise glucose <100 mg/dL (5.6 mmol/L): Ingest added carbohydrate, depending on ability to lower insulin doses during workout, time of day, and intensity/duration of activity 1
• Post-exercise hypoglycemia: May occur and last for several hours due to increased insulin sensitivity 1
• Proper footwear and daily foot examination are mandatory for all individuals with peripheral neuropathy 1

Critical Pitfalls to Avoid

• Never delay treatment intensification when patients fail to meet glycemic targets after 3 months—therapeutic inertia worsens long-term outcomes 2, 4, 3
• Never delay adding SGLT2 inhibitor or GLP-1 receptor agonist in patients with established cardiovascular disease, heart failure, or chronic kidney disease 2, 3
• Never continue sulfonylureas once SGLT2 inhibitors or GLP-1 agonists achieve glycemic control—they increase hypoglycemia risk without mortality benefit 2, 4
• Never target HbA1c below 6.5%—this requires immediate deintensification 2, 4
• Never use DPP-4 inhibitors as they lack mortality benefit and should not be combined with GLP-1 agonists 2, 4
• Never neglect ongoing lifestyle modifications throughout the entire treatment course regardless of medication regimen 3
• Never allow more than 2 days to elapse between exercise sessions to decrease insulin resistance 1

Special Populations: Older Adults and End-of-Life Care

Older Adults in Long-Term Care:

• Alert provider immediately for blood glucose <70 mg/dL (3.9 mmol/L) 1
• Call as soon as possible for glucose 70-100 mg/dL (regimen may need adjustment), >250 mg/dL within 24 hours, or >300 mg/dL over 2 consecutive days 1

Palliative Care Patients:

• Stable patient: Continue previous regimen, focus on preventing hypoglycemia and hyperglycemia, keeping levels below renal threshold 1
• Patient with organ failure: Preventing hypoglycemia is of greater significance; reduce insulin doses as oral intake decreases but do not stop in type 1 diabetes; reduce hypoglycemia-causing agents in type 2 diabetes 1
• Dying patient: For type 2 diabetes, discontinuation of all medications may be reasonable; for type 1 diabetes, small amount of basal insulin may maintain glucose levels and prevent acute hyperglycemic complications 1