What is the guideline for management (GDMT) of diabetes?

Guideline-Directed Medical Therapy (GDMT) for Diabetes

For adults with type 2 diabetes, start metformin plus lifestyle modifications immediately at diagnosis, then add an SGLT-2 inhibitor or GLP-1 receptor agonist when glycemic control remains inadequate—prioritizing SGLT-2 inhibitors for patients with heart failure or chronic kidney disease, and GLP-1 agonists for those with high stroke risk or requiring weight loss. 1, 2

Initial Management Strategy

First-Line Therapy

• Begin metformin 500-850 mg once or twice daily with meals at diagnosis unless contraindicated, combined with lifestyle modifications targeting 5-10% weight loss and 150 minutes weekly of moderate-intensity aerobic activity 1, 2, 3
• Metformin remains the cornerstone based on cardiovascular mortality benefits demonstrated in the UKPDS, showing 36% reduction in all-cause mortality and 39% reduction in myocardial infarction 4
• Titrate metformin to maximum tolerated dose (typically 2000 mg daily) over 3 months before adding second-line therapy 3

Glycemic Targets

• Target HbA1c between 7-8% for most adults with type 2 diabetes 1, 2
• Deintensify treatment when HbA1c falls below 6.5% to reduce hypoglycemia risk 1
• Individualize targets based on hypoglycemia risk, life expectancy, diabetes duration, established vascular complications, and major comorbidities 1
• Monitor HbA1c every 3 months until target achieved, then every 6 months once stable 3

Second-Line Therapy Algorithm

When to Add Second Agent

• Add therapy when HbA1c remains above target after 3 months on maximum tolerated metformin dose 3
• The American College of Physicians strongly recommends adding either an SGLT-2 inhibitor OR a GLP-1 agonist (not both initially) 1, 2

Medication Selection Based on Comorbidities

Prioritize SGLT-2 inhibitors when:

• Heart failure is present or patient is at high risk—reduces hospitalization for congestive heart failure 1, 2
• Chronic kidney disease is present—reduces CKD progression by 24-39% 1, 3
• Patient needs reduction in all-cause mortality and major adverse cardiovascular events 1, 2

Prioritize GLP-1 receptor agonists when:

• High stroke risk exists—reduces stroke incidence 1, 2
• Significant weight loss is a treatment priority 1, 2
• Patient needs reduction in all-cause mortality and major adverse cardiovascular events 1, 2

Avoid DPP-4 inhibitors:

• The American College of Physicians strongly recommends AGAINST adding DPP-4 inhibitors to metformin as they do not reduce mortality or morbidity 1, 2

Cardiovascular Risk Reduction

• For patients with established cardiovascular disease, chronic kidney disease, or very high cardiovascular risk, add SGLT-2 inhibitor or GLP-1 agonist regardless of HbA1c level 3
• Empagliflozin or liraglutide specifically reduce risk of death in high-risk populations 3

Critical Management Adjustments

When Adding SGLT-2 Inhibitors or GLP-1 Agonists

• Reduce or discontinue sulfonylureas and long-acting insulins when adequate glycemic control is achieved to prevent severe hypoglycemia 1, 2
• This is a common pitfall—failure to deintensify older agents leads to dangerous hypoglycemia 2
• Sulfonylureas and long-acting insulins are inferior for mortality/morbidity reduction but retain limited value for glycemic control alone 1, 2

Glucose Monitoring

• Self-monitoring of blood glucose may be unnecessary in patients on metformin plus SGLT-2 inhibitor or GLP-1 agonist, as these combinations carry minimal hypoglycemia risk 1, 2
• Reserve frequent monitoring (≥4 times daily) for patients on multiple daily insulin injections or insulin pump therapy 1

Type 1 Diabetes Management

Treat all patients with type 1 diabetes using multiple daily insulin injections (≥3 injections daily) or continuous subcutaneous insulin infusion to reduce microvascular complications and cardiovascular disease 1

Insulin Regimen

• Use insulin analogues rather than regular insulin to reduce hypoglycemia risk 1
• Match prandial insulin doses to carbohydrate intake, preprandial glucose levels, and anticipated activity 1
• Consider continuous glucose monitoring to reduce severe hypoglycemia risk, especially in patients with hypoglycemia unawareness 1

Pediatric Type 2 Diabetes (Ages 10-18)

Initial Treatment

• Initiate insulin immediately for children presenting with ketosis or diabetic ketoacidosis 1
• For non-ketotic presentations, start metformin alongside lifestyle modifications rather than lifestyle changes alone 1
• Integrate diet and exercise with medication from the outset—isolated lifestyle intervention is insufficient 1

Comprehensive Care Components

Team-Based Approach

• Coordinate care through physician-led teams including nurse practitioners, nurses, dietitians, pharmacists, and mental health professionals 1
• Involve clinical pharmacists to reduce polypharmacy risks 1, 2
• Ensure diabetes self-management education is integral to all care plans 1

Comorbidity Management

• Initiate antihypertensive treatment when BP >140/90 mmHg, targeting SBP 130 mmHg and DBP <80 mmHg 3
• Start moderate-intensity statin for all adults 40-75 years with diabetes; use high-intensity statin for those with multiple ASCVD risk factors 3
• Target LDL-C reduction ≥30% for moderate CV risk and ≥50% for high/very high CV risk 3

Social Determinants

• Assess social risk factors systematically and connect patients to community services 1
• Address cost barriers—discuss medication expenses when selecting SGLT-2 inhibitors or GLP-1 agonists, as no generic formulations currently exist 1, 2

Diabetes Prevention

For very high-risk individuals with combined impaired glucose tolerance and impaired fasting glucose plus additional risk factors:

• Consider metformin for prevention, particularly in those with BMI ≥35 kg/m² and age <60 years 1
• Lifestyle modifications targeting 5-10% weight loss and 30 minutes daily moderate activity remain primary prevention strategy 1