What is the recommended management for an adult with type 2 diabetes?

Management of Type 2 Diabetes in Adults

Start metformin immediately at diagnosis combined with lifestyle modifications, then add a GLP-1 receptor agonist or SGLT-2 inhibitor after 3 months if HbA1c remains above 7%, selecting the agent based on comorbidities rather than glycemic control alone. 1, 2

Initial Pharmacologic Management

• Metformin is mandatory first-line therapy for all adults with type 2 diabetes unless contraindicated, and must be continued long-term as the foundation of treatment 1, 2, 3
• Start metformin at low doses (500 mg once or twice daily) and titrate gradually to minimize gastrointestinal side effects; advise patients to take with food or 15 minutes after meals if symptoms persist 2
• Monitor vitamin B12 levels periodically during long-term metformin use, particularly in patients developing anemia or peripheral neuropathy 4, 1, 2

Glycemic Targets

• Target HbA1c between 7-8% for most adults with type 2 diabetes 1, 5, 2
• Immediately deintensify treatment if HbA1c falls below 6.5% to prevent hypoglycemia and overtreatment 1, 5, 2
• For young adults (20-30 years) with recent-onset diabetes, no comorbidities, and expected lifespan >50 years, target HbA1c <6.5% using low-hypoglycemia-risk agents 5
• For elderly patients (≥65 years) with limited life expectancy (<10 years) or extensive comorbidities, target HbA1c 7.5-8.0% 5

Lifestyle Modifications

• Restrict calorie intake to 1500 kcal/day 1, 5, 2
• Limit dietary fat to 30-35% of total energy intake and target carbohydrates at 50-65% of total calories 2
• Maintain protein intake at approximately 0.8 g/kg/day 2
• Engage in at least 150 minutes per week of moderate-intensity aerobic exercise spread over at least 3 days with no more than 2 consecutive days without activity 4, 1, 2
• Perform 2-3 sessions per week of resistance exercise on nonconsecutive days 4, 1, 2
• Interrupt prolonged sitting every 30 minutes for blood glucose benefits 4

Second-Line Therapy Algorithm

After 3 months of metformin plus lifestyle modifications, if HbA1c remains above 7%, add either an SGLT-2 inhibitor or GLP-1 receptor agonist based on the following criteria: 1, 2

Choose SGLT-2 Inhibitor When:

• Patient has heart failure (any ejection fraction category) - reduces heart failure hospitalizations by 18-25% 1, 5
• Patient has chronic kidney disease with eGFR 20-60 mL/min/1.73 m² and/or albuminuria - slows CKD progression by 24-39% 1, 5, 3
• Cardiovascular mortality reduction is the primary goal 1
• Note: Glycemic efficacy diminishes when eGFR <45 mL/min/1.73 m²; use primarily for organ protection in this range 5

Choose GLP-1 Receptor Agonist When:

• Patient has elevated stroke risk - reduces stroke incidence by 12-26% 5
• Substantial weight loss is a therapeutic priority - high-potency GLP-1 RAs achieve >5% body weight loss in most users 5, 3
• Patient has advanced CKD with eGFR <30 mL/min/1.73 m² (when SGLT-2 inhibitor not suitable) - carries low hypoglycemia risk 1, 5
• All-cause mortality reduction is the primary goal 1

For Patients with BMI >25:

• Tirzepatide is the preferred GLP-1 receptor agonist, achieving mean weight loss of 8.47 kg with approximately 67% of patients achieving ≥10% weight reduction 1, 5
• Tirzepatide demonstrates superior glycemic control compared to other GLP-1 receptor agonists in head-to-head trials 5

Medication Review and Adjustment

• Reassess the medication regimen every 3-6 months, adjusting for glycemic control, weight objectives, metabolic comorbidities, and hypoglycemia risk 1, 5, 2
• Test HbA1c every 3 months to evaluate treatment response 2

Cardiovascular Risk Management

Lipid Management:

• Prescribe moderate-intensity statin therapy to all adults aged 40-75 years with diabetes, regardless of 10-year ASCVD risk 2, 3
• For patients with established atherosclerotic cardiovascular disease, target LDL-cholesterol <70 mg/dL using high-intensity statin therapy 1, 2, 3
• Statin therapy reduces coronary heart disease events by 19-42% in people with diabetes 1

Blood Pressure Management:

• Target systolic/diastolic <140/80 mmHg for most adults with diabetes 1
• ACE-inhibitors or ARBs are the preferred first-line agents, especially in the presence of albuminuria 1
• Aggressive blood pressure lowering halves the risk of cardiovascular events 1

Aspirin Therapy:

• For primary prevention, prescribe aspirin 75-162 mg/day only when 10-year cardiovascular risk exceeds 10% (men >50 years or women >60 years with at least one additional major risk factor) 1
• For secondary prevention, prescribe aspirin 75-162 mg/day in all patients with diabetes and a history of cardiovascular disease 1
• Use clopidogrel 75 mg/day in patients with documented aspirin allergy 1

Insulin Therapy

• Approximately one-third of adults with type 2 diabetes will require insulin at some point during their disease course 5, 3
• Consider early introduction of insulin if there is evidence of ongoing catabolism (weight loss), symptoms of hyperglycemia, or when HbA1c >10% or blood glucose ≥300 mg/dL 4
• When initiating insulin, begin with basal insulin (long-acting) once daily, alone or in combination with oral agents 6
• Continue metformin when starting insulin therapy for ongoing glycemic and metabolic benefits, as this combination is associated with decreased weight gain, lower insulin dose, and less hypoglycemia 4, 6
• Titrate basal insulin using fasting plasma glucose values 6

Cost-Constrained Situations

When newer agents (SGLT-2 inhibitors, GLP-1 receptor agonists) are unaffordable:

• Maximize glipizide dose as second-line therapy 1, 5, 2
• If HbA1c remains >8% after maximizing glipizide, add basal insulin 1, 5, 2
• Immediately reduce glipizide dose by 50% when adding insulin to prevent severe hypoglycemia 1, 5, 2

Critical Pitfalls to Avoid

• Do not delay treatment intensification when patients fail to meet glycemic targets after 3 months - therapeutic inertia worsens long-term outcomes 1, 5, 2
• Do not continue sulfonylureas once SGLT-2 inhibitors or GLP-1 agonists achieve glycemic control - they increase hypoglycemia risk without mortality benefit 1, 5, 2
• Do not use DPP-4 inhibitors as second-line agents - they lack mortality and morbidity benefits compared with SGLT-2 inhibitors or GLP-1 RAs 1, 5
• Do not combine tirzepatide with DPP-4 inhibitors - this provides no additional glucose lowering beyond tirzepatide alone 5, 2
• Do not target HbA1c below 6.5% - this requires immediate deintensification 1, 5, 2
• Do not abruptly discontinue oral medications when starting insulin due to risk of rebound hyperglycemia 6

Complication Screening and Prevention

• Perform initial retinopathy examination within 3-5 years of type 1 diabetes diagnosis and shortly after type 2 diabetes diagnosis, then annually 2
• Assess eGFR and albuminuria every 3-6 months with medication adjustments as needed 2
• Tight glycemic control reduces microvascular complications including retinopathy and nephropathy by 3.5% absolute risk reduction 3
• Intensive glucose-lowering strategies (HbA1c <7%) reduce myocardial infarction by 3.3-6.2% and mortality by 2.7-4.9% over 2 decades 3

Special Populations

Older Adults with Advanced Disease:

For stable patients: Continue previous regimen focusing on hypoglycemia prevention and keeping glucose levels below renal threshold; there is no role for aggressive HbA1c lowering 4, 2

For patients with organ failure: Preventing hypoglycemia is of greatest significance; in type 2 diabetes, reduce doses of agents that may cause hypoglycemia; allow glucose values in the upper level of the desired target range 4, 2

For dying patients: For type 2 diabetes, discontinuation of all medications may be reasonable as patients are unlikely to have oral intake 4

Sodium and Alcohol Intake

• Limit sodium consumption to <2,300 mg/day; restriction below 1,500 mg is generally not recommended even for those with hypertension 4
• Moderate alcohol intake (no more than one drink per day for women, two for men) ingested with food does not have major detrimental effects on long-term blood glucose management 4