How to manage difficult to control diabetes mellitus?

Management of Difficult-to-Control Diabetes Mellitus

For patients with difficult-to-control diabetes, intensify therapy by adding a second agent to metformin (or initiating insulin if markedly symptomatic with glucose ≥250 mg/dL or HbA1c ≥8.5%), while simultaneously addressing psychosocial barriers, optimizing lifestyle interventions, and screening for complications that may be contributing to poor control. 1, 2

Initial Assessment and Root Cause Analysis

When encountering difficult-to-control diabetes, systematically evaluate the following factors:

Verify Inadequate Control

• Measure HbA1c quarterly in patients not meeting glycemic goals (versus twice yearly for stable patients) 1, 3
• Confirm that home glucose monitoring correlates with HbA1c values, as discrepancies may indicate red blood cell turnover issues or inaccurate reporting 1
• Use point-of-care A1C testing to enable more timely treatment adjustments 1

Identify Barriers to Control

• Screen for psychosocial problems including depression, diabetes-related distress, anxiety, eating disorders, and cognitive impairment when self-management is poor 1
• Assess medication adherence, financial resources, social support, and health literacy 1, 2
• Evaluate whether the patient has received diabetes self-management education (DSME), as this improves clinical outcomes and should be provided at diagnosis and critical care points 4

Pharmacologic Intensification Strategy

For Patients on Monotherapy (Typically Metformin)

• If noninsulin monotherapy at maximal tolerated dose does not achieve or maintain A1C target over 3-6 months, add a second oral agent, a GLP-1 receptor agonist, or insulin 1
• Consider SGLT2 inhibitors (like empagliflozin) which provide additional cardiovascular and weight loss benefits 5, 6
• GLP-1 receptor agonists offer glucose control plus weight reduction and improved cardiovascular outcomes 6

For Markedly Uncontrolled Patients

• In newly diagnosed or poorly controlled patients with blood glucose ≥250 mg/dL, HbA1c ≥8.5%, or marked symptoms, initiate basal insulin immediately while starting or continuing metformin 1, 2
• Starting insulin dose ranges from 0.25 to 1.0 units/kg/day, with 0.5 units/kg typical for metabolically stable patients 1, 7

For Patients Already on Multiple Agents

• Add basal insulin if not already prescribed, as combination therapy with insulin plus oral agents improves glycemic control 5
• When adding insulin to existing therapy, empagliflozin 10-25 mg daily reduces HbA1c by an additional 0.6-0.7% and promotes weight loss of 1.7-3.0% 5

Lifestyle Intervention Optimization

Medical Nutrition Therapy

• Prescribe individualized meal planning with a registered dietitian familiar with diabetes medical nutrition therapy 1, 2
• For overweight/obese patients, implement high-intensity diet and behavioral therapy targeting ≥5% weight loss with a 500-750 kcal/day energy deficit 1, 2
• Teach carbohydrate counting and its impact on blood glucose 3

Physical Activity

• Advise at least 150 minutes/week of moderate-intensity aerobic activity (50-70% maximum heart rate), spread over at least 3 days with no more than 2 consecutive days without exercise 1
• Encourage resistance training at least twice per week 1
• Provide strategies for safe exercise with diabetes, including adjustments for hypoglycemia prevention 3

Address Comorbidities and Complications

Blood Pressure Management

• Measure blood pressure at every diabetes visit 1
• Target systolic BP <130 mmHg and diastolic BP <80 mmHg for most patients 1
• Patients with BP 130-139/80-89 mmHg may receive lifestyle therapy for maximum 3 months before adding pharmacologic agents 1
• Those with BP ≥140/90 mmHg require immediate pharmacologic treatment 1

Screen for Complications

• Perform annual comprehensive eye examination, annual diabetic kidney disease screening (urine albumin-to-creatinine ratio and kidney function tests), and annual comprehensive foot examination 2
• Undiagnosed or undertreated complications may contribute to poor glycemic control 2

Immunizations

• Provide annual influenza vaccine to all diabetic patients ≥6 months of age 1
• Administer pneumococcal polysaccharide vaccine to all diabetic patients ≥2 years of age 1
• Administer hepatitis B vaccination per CDC recommendations 1

Hypoglycemia Prevention and Management

A critical pitfall in intensifying therapy is causing hypoglycemia, which worsens outcomes and quality of life:

• Prescribe glucagon for all individuals at significant risk of severe hypoglycemia and instruct caregivers in its administration 1
• Patients with hypoglycemia unawareness or severe hypoglycemic episodes should raise glycemic targets to strictly avoid further hypoglycemia for at least several weeks 1
• Treat conscious hypoglycemia with 15-20 g glucose, recheck in 15 minutes, and repeat if needed 1

Adjust Glycemic Targets Based on Patient Characteristics

Less stringent A1C goals (such as <8%) are appropriate for patients with:

• History of severe hypoglycemia 1
• Limited life expectancy 1
• Advanced microvascular or macrovascular complications 1
• Extensive comorbid conditions 1
• Long-standing diabetes where the <7% goal is difficult to achieve despite intensive efforts 1

Consider Bariatric Surgery

For adults with BMI >35 kg/m² and type 2 diabetes, bariatric surgery may be considered, especially if diabetes or associated comorbidities are difficult to control with lifestyle and pharmacologic therapy 1

• Patients require lifelong lifestyle support and medical monitoring post-surgery 1
• Insufficient evidence exists to recommend surgery for BMI 30-35 kg/m² outside research protocols 1

Implement Team-Based Care

• Diabetes care should be managed by a multidisciplinary team including physicians, nurse practitioners, nurses, dietitians, pharmacists, and mental health professionals 2
• Patients must assume an active role in their care as part of this collaborative approach 4
• Use patient-centered communication with active listening and assessment of literacy and barriers to care 2

Common Pitfalls to Avoid

• Do not use sliding-scale insulin alone for hospitalized patients, as basal-bolus regimens produce superior outcomes 1
• Do not overlook depression screening, as depression significantly impacts glycemic control and occurs frequently in diabetes 3
• Do not delay insulin initiation in markedly symptomatic patients while attempting multiple oral agent combinations 1, 2
• Do not pursue overly aggressive targets in patients with history of severe hypoglycemia, as avoiding hypoglycemia takes precedence over achieving lower HbA1c 1