What are the current guidelines for diagnosing and managing diabetes in adults, covering initial evaluation, first-line treatment, therapeutic targets, and stepwise medication intensification?

Diabetes Management Guidelines for Adults

Diagnosis

Diagnose diabetes with a fasting plasma glucose ≥126 mg/dL (7.0 mmol/L) confirmed on two separate occasions, or HbA1c ≥6.5% confirmed by a plasma glucose-specific test. 1

• Screen all adults starting at age 45 and repeat every 3 years if normal 2
• Screen earlier and more frequently if risk factors present: obesity, first-degree relative with diabetes, hypertension, hypertriglyceridemia, or previous impaired glucose homeostasis 2
• HbA1c 6.5-6.9% confirmed by fasting plasma glucose or oral glucose tolerance test establishes diabetes diagnosis 1
• HbA1c ≥7.0% confirmed by repeat HbA1c or plasma glucose test also establishes diagnosis 1

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Type 1 Diabetes Management

Insulin Therapy

Treat all adults with type 1 diabetes using continuous subcutaneous insulin infusion (insulin pump) or multiple daily injections of prandial plus basal insulin. 3

• Insulin analogs or inhaled insulin are strongly preferred over human insulins to minimize hypoglycemia risk 3
• Automated insulin delivery systems should be offered to all adults with type 1 diabetes 3
• Typical regimens consist of basal insulin (50% of total daily dose) plus prandial insulin with meals 3

Glucose Monitoring

Implement continuous glucose monitoring early in all adults with type 1 diabetes to improve glycemic outcomes, quality of life, and minimize hypoglycemia. 3

• Monitor capillary blood glucose ≥3 times daily in patients not using continuous glucose monitoring 3
• Check A1C at least twice yearly in patients meeting goals, quarterly if therapy changed or goals not met 3

Patient Education

Educate all patients on matching mealtime insulin to carbohydrate, fat, and protein intake, plus correction dosing based on current glucose, trends, sick days, and anticipated activity. 3

• Prescribe glucagon for all individuals taking insulin; train family/caregivers on administration 3
• Glucagon preparations not requiring reconstitution are preferred 3

Medication Review

Reassess insulin treatment plans every 3-6 months and adjust based on glycemic control, hypoglycemia risk, and individual factors. 3, 4

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Type 2 Diabetes Management

First-Line Therapy

Initiate metformin immediately at diagnosis combined with lifestyle modifications in all adults with type 2 diabetes unless contraindicated. 4, 5, 6

• Continue metformin long-term as foundation of therapy 4, 5
• Monitor vitamin B12 levels during long-term use, especially if anemia or peripheral neuropathy develops 4, 5, 6

Lifestyle Modifications

Prescribe 1500 kcal/day calorie restriction with fat limited to 30-35% of total energy intake. 4, 5

• Require 150 minutes weekly of moderate-intensity aerobic exercise 4, 5
• Add 2-3 sessions weekly of resistance exercise on nonconsecutive days 4, 5
• Target minimum 30 minutes of physical activity at least 5 times weekly 4, 5

Second-Line Therapy: Organ-Protection Algorithm

When metformin plus lifestyle fails to achieve HbA1c target after 3 months, select second agent based on comorbidities rather than glycemia alone. 4, 6

SGLT2 Inhibitor Preferred When:

• Patient has heart failure (any ejection fraction category) 3, 4, 6
• Patient has CKD with eGFR 20-60 mL/min/1.73 m² and/or albuminuria 3, 4, 6
• Goal is cardiovascular mortality reduction 4
• Note: Glycemic benefit diminishes when eGFR <45 mL/min/1.73 m² 3
• SGLT2 inhibitors slow CKD progression, lower cardiovascular events, and reduce heart failure hospitalizations 4

GLP-1 Receptor Agonist Preferred When:

• Patient has heightened stroke risk 4, 6
• Substantial weight loss is therapeutic priority 4, 6
• Advanced CKD with eGFR <30 mL/min/1.73 m² (when SGLT2 not suitable) 3, 4
• Goal is all-cause mortality reduction 4
• GLP-1 agonists are preferred over insulin (Grade A recommendation) 6

For Patients with BMI >25:

Tirzepatide is favored as second-line agent, achieving mean weight loss of 8.5 kg with approximately 67% of patients achieving ≥10% weight reduction. 4, 5

• Tirzepatide demonstrates superior glycemic control compared to other GLP-1 receptor agonists in head-to-head trials 5

Glycemic Targets

Target HbA1c 7-8% for most adults with type 2 diabetes. 4, 6

• Tighter target of 6.0-7.0% may be used in individuals with life expectancy >10-15 years, minimal microvascular disease, and when safely achievable 4
• Looser target of 8.0-9.0% appropriate for those with life expectancy <5 years, significant comorbidities, or advanced complications 4
• Deintensify treatment immediately when HbA1c falls below 6.5% to avoid hypoglycemia and overtreatment 4, 5, 6

Medication Reassessment

Reevaluate medication plan every 3-6 months and adjust based on glycemic control, weight goals, metabolic comorbidities, and hypoglycemia risk. 4, 5, 6

• Do not delay treatment intensification when patients fail to meet targets after 3 months—therapeutic inertia worsens outcomes 4, 5

Cost-Constrained Situations

When newer agents are unaffordable, maximize glipizide dose. 4

• If HbA1c remains >8% after maximizing glipizide, add basal insulin 4
• Immediately reduce glipizide dose by 50% when adding insulin to prevent severe hypoglycemia 4
• Discuss medication costs when selecting from SGLT2 inhibitors or GLP-1 agonists; prescribe generics when available 6

Critical Pitfalls to Avoid

Discontinue sulfonylureas once SGLT2 inhibitors or GLP-1 agonists achieve adequate glycemic control—they increase severe hypoglycemia risk without mortality benefit. 4, 6

• Do not combine tirzepatide with DPP-4 inhibitors as this provides no additional glucose lowering 5
• Do not use DPP-4 inhibitors as monotherapy—they lack mortality benefit 4
• Do not target HbA1c below 6.5%—this requires deintensification 4, 5, 6

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Cardiovascular Risk Management

Lipid Management

Obtain lipid profile at diabetes diagnosis, initial evaluation, and every 5 years thereafter if age <40. 3

• For adults aged 40-75 without atherosclerotic cardiovascular disease (ASCVD), use moderate-intensity statin plus lifestyle therapy 3
• For adults aged 40-75 at higher cardiovascular risk, use high-intensity statin to reduce LDL ≥50% from baseline and target LDL <70 mg/dL 3
• For all ages with diabetes and established ASCVD, use high-intensity statin targeting LDL reduction ≥50% and LDL goal <55 mg/dL 3
• Add ezetimibe or PCSK9 inhibitor if LDL goal not achieved on maximum tolerated statin 3
• For adults >75 years already on statin, continue treatment 3
• For adults >75 years not on statin, consider initiating moderate-intensity statin after discussing benefits and risks 3

Blood Pressure Management

Target blood pressure <130/80 mmHg for most adults with diabetes. 3, 4

• Aggressive blood pressure lowering halves cardiovascular event risk 4
• In patients >60 years with isolated systolic hypertension, aggressive treatment reduces cardiovascular events by 34-69% 4
• ACE inhibitors or ARBs are preferred first-line agents, especially with albuminuria 3, 4

Aspirin Therapy

For secondary prevention, prescribe aspirin 75-162 mg/day in all patients with diabetes and history of cardiovascular disease. 4

• For primary prevention, use aspirin only when 10-year cardiovascular risk exceeds 10% (men >50 years or women >60 years with ≥1 additional major risk factor) 4
• Avoid aspirin for primary prevention in low-risk individuals (10-year risk <5%) because bleeding risk outweighs benefit 4
• Use clopidogrel 75 mg/day in patients with documented aspirin allergy 4

Dyslipidemia Management

Intensify lifestyle therapy and optimize glycemic control for elevated triglycerides (≥150 mg/dL) and/or low HDL (<40 mg/dL men, <50 mg/dL women). 3

• Recommend Mediterranean or DASH eating pattern, reducing saturated and trans fat, increasing plant stanols/sterols, omega-3 fatty acids, and viscous fiber 3

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Microvascular Complication Screening

Retinopathy

Perform annual retinal examinations by licensed eye care professional for all patients with diabetes. 3

• Visual changes not explained by acute glycemic fluctuations require prompt ophthalmologic evaluation 3

Nephropathy

Obtain annual spot urine microalbumin-to-creatinine ratio. 3

• Use ACE inhibitors or ARBs for all patients with albuminuria 3
• SGLT2 inhibitors slow CKD progression and reduce cardiovascular events in patients with eGFR 20-60 mL/min/1.73 m² and/or albuminuria 4

Neuropathy

Perform comprehensive foot examination annually to identify ulcer and amputation risk factors. 3

• Refer patients with insensate foot, open foot lesion, or history of lesion to podiatrist or vascular surgeon 3
• Provide special shoes as recommended by licensed professionals to aid healing and prevent new lesions 3

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Special Populations

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

In adults with type 2 diabetes, MASLD, and overweight/obesity, use GLP-1 RA or dual GIP/GLP-1 RA for glycemic management and weight loss. 3

• In patients with biopsy-proven MASH or high risk for liver fibrosis, prefer pioglitazone, GLP-1 RA, or dual GIP/GLP-1 RA for beneficial effects on MASH 3