What is the best course of treatment for a female patient with uncontrolled type 2 diabetes (T2D), hypertension, and hyperlipidemia, who has a history of poor compliance, impaired renal function, and elevated HbA1c, currently on Novolin N (NPH insulin) 30 units subcutaneously (SQ) every hour of sleep (q hs), pioglitazone (thiazolidinedione) 30 mg once a day, glucotrol XL (glipizide) 10 mg twice a day, and Novolin R (regular insulin) sliding scale?

Immediate Insulin Intensification Required for Severely Uncontrolled Type 2 Diabetes

This patient with HbA1c 14.1% requires immediate aggressive insulin intensification with a basal-bolus regimen, discontinuation of glipizide, continuation of metformin if not contraindicated by renal function, and strong consideration for adding an SGLT2 inhibitor or GLP-1 receptor agonist once glycemic control improves. 1, 2

Critical Assessment of Current Regimen Failure

• The current regimen has catastrophically failed, with HbA1c rising from 13.7% to 14.1% despite being on NPH insulin, glipizide, pioglitazone, and sliding scale regular insulin 1
• At HbA1c >10%, patients require insulin therapy to prevent metabolic decompensation and achieve rapid glycemic control 2
• Sliding scale insulin alone is strongly discouraged and ineffective for glycemic management, as it only treats hyperglycemia reactively rather than preventing it 2
• The eGFR of 66 mL/min/1.73m² indicates Stage 2 chronic kidney disease, requiring careful medication selection 3

Immediate Treatment Plan

Step 1: Insulin Regimen Overhaul

• Discontinue the current NPH 30 units at bedtime and sliding scale regular insulin regimen immediately 2
• Initiate basal insulin (long-acting analog like glargine or degludec) at 0.2 units/kg/day given the severity of hyperglycemia 1, 2
• Add prandial rapid-acting insulin (lispro, aspart, or glulisine) starting with 4 units before each meal or 10% of the basal dose per meal 2
• Increase basal insulin by 2-4 units every 3-7 days until fasting glucose reaches 80-130 mg/dL 1, 2
• Titrate prandial insulin by 1-2 units or 10-15% twice weekly based on 2-hour postprandial glucose readings 2

Step 2: Oral Medication Adjustments

• Discontinue glipizide (Glucotrol XL) immediately—sulfonylureas must be stopped when moving to complex insulin regimens beyond basal insulin due to significantly increased hypoglycemia risk 2
• Continue metformin if eGFR remains >45 mL/min/1.73m², as it provides complementary glucose-lowering, reduces total insulin requirements, and offers cardiovascular benefits 3, 1, 2
• Consider discontinuing pioglitazone due to the combination with insulin causing 10-20% risk of drug-related congestive heart failure and severe edema 4
• If pioglitazone is continued, reduce to 15 mg daily or even 7.5 mg daily to minimize fluid retention risk when combined with insulin 4

Step 3: Add Cardioprotective Agent Once Stabilized

• After achieving HbA1c <10% with insulin intensification (typically 3 months), strongly consider adding an SGLT2 inhibitor (empagliflozin 10-25 mg or canagliflozin 100-300 mg) for cardiovascular and renal protection 3, 1, 5, 6
• SGLT2 inhibitors provide additional HbA1c reduction of 0.6-0.8%, reduce cardiovascular events, slow progression of diabetic nephropathy, and cause weight loss rather than weight gain 1, 5, 6
• With established hypertension and Stage 2 CKD, this patient has indicators of high cardiovascular risk warranting SGLT2 inhibitor therapy independent of HbA1c 3
• Alternative: GLP-1 receptor agonist if SGLT2 inhibitor contraindicated, providing HbA1c reduction of 2-2.5% with weight loss benefits 1

Monitoring Protocol

• Check blood glucose before each meal and at bedtime daily during insulin titration 2
• Recheck HbA1c in 3 months—if still >7%, further intensification required 1, 7
• Monitor for hypoglycemia vigilantly, especially 2-4 hours after prandial insulin when action peaks 2
• Assess for edema weekly if continuing pioglitazone with insulin 4
• Recheck renal function (eGFR, urine albumin-to-creatinine ratio) in 3 months 3

Critical Pitfalls to Avoid

• Do not delay insulin intensification waiting for oral agents to work—at HbA1c 14.1%, only aggressive insulin therapy can reduce HbA1c to target, as most oral agents reduce HbA1c by <1% 2
• Do not continue sulfonylureas with basal-bolus insulin—this dramatically increases hypoglycemia risk without additional benefit 2
• Do not rely on sliding scale insulin without optimizing basal insulin first—this approach is ineffective for long-term management 2
• Do not add pioglitazone at full dose (30 mg) with intensive insulin—this combination causes severe edema and heart failure in 10-20% of patients 4
• Prolonged severe hyperglycemia (months at HbA1c >9%) must be specifically avoided due to increased complication risk and progressive beta-cell failure 2

Addressing Compliance Barriers

• Given the history of poor compliance and refusal of endocrinology referral due to transportation, consider:
  • Telemedicine endocrinology consultation if available 1
  • Diabetes educator involvement for insulin injection technique and self-monitoring training 2
  • Simplified twice-daily premixed insulin regimen (70/30 or 75/25) as alternative if adherence to basal-bolus is not feasible, though this offers less flexibility 2
  • Written instructions for insulin dose adjustments based on glucose patterns 2

Expected Outcomes

• With aggressive insulin intensification, expect HbA1c reduction of 3-4% over 3 months, bringing HbA1c from 14.1% to approximately 10-11% 1, 2
• Further reduction to target <7-8% will require continued titration and likely addition of SGLT2 inhibitor or GLP-1 receptor agonist 1, 7
• Less stringent target of HbA1c <8% may be appropriate given history of poor compliance and to reduce hypoglycemia risk 3, 7