What medication is recommended for managing hyperglycemia, hypertension, and hypothyroidism?

Medication Management for Hyperglycemia, Hypertension, and Hypothyroidism

Hyperglycemia Management

For hyperglycemia in type 2 diabetes, initiate metformin as first-line therapy unless contraindicated, and if injectable therapy becomes necessary, prioritize GLP-1 receptor agonists over insulin due to superior cardiovascular benefits, weight reduction, and lower hypoglycemia risk. 1

First-Line Oral Therapy

• Metformin is the optimal first-line drug for type 2 diabetes unless contraindications exist, offering the most cost-effective glucose control 1
• Start metformin at a low dose with gradual titration to minimize gastrointestinal side effects 1
• Metformin primarily reduces hepatic glucose production and improves insulin sensitivity without increasing hypoglycemia risk 2

When to Intensify Beyond Metformin

• If HbA1c remains above target on metformin monotherapy, add a second agent based on patient characteristics 1
• For patients with HbA1c ≥9.0% at presentation, consider starting combination therapy immediately rather than sequential monotherapy 1
• For patients with extreme hyperglycemia (glucose >300-350 mg/dL or HbA1c ≥10-12%), insulin therapy should be strongly considered from the outset 1

Second-Line Oral Agent Selection

For patients requiring a second oral agent after metformin:

• DPP-4 inhibitors (sitagliptin, linagliptin) provide moderate glucose-lowering (HbA1c reduction 0.4-0.9%) with minimal hypoglycemia risk and weight-neutral effects 3, 2
• Linagliptin is preferred over other DPP-4 inhibitors in renal impairment as it requires no dose adjustment regardless of kidney function, while sitagliptin requires dose reduction when eGFR <45 mL/min/1.73 m² 3
• Avoid saxagliptin in patients with heart failure risk due to 27% increased risk of heart failure hospitalization demonstrated in the SAVOR TIMI-53 trial 3
• Sitagliptin and linagliptin showed neutral cardiovascular effects in TECOS and CARMELINA trials respectively 3

Injectable Therapy: GLP-1 Receptor Agonists vs Insulin

When injectable therapy is needed, GLP-1 receptor agonists are the preferred first injectable medication over insulin 1

GLP-1 receptor agonist advantages:

• Similar or superior HbA1c reduction compared to insulin (up to 1.6% reduction) 1, 4, 5
• Weight loss of 1.8-3.4 kg versus weight gain with insulin 1, 4, 5
• Lower hypoglycemia risk compared to insulin 1
• Once-weekly formulations available (semaglutide, dulaglutide, exenatide once-weekly) versus daily or more frequent insulin injections 6
• Proven cardiovascular benefit in patients with pre-existing atherosclerotic vascular disease 6

Liraglutide-specific dosing:

• Start at 0.6 mg daily for at least 1 week to improve gastrointestinal tolerability 7
• Increase to 1.2 mg daily, with option to escalate to maximum 1.8 mg daily for additional benefit 7
• Can be administered at any time of day, independent of meals 7
• When combined with metformin and glimepiride, liraglutide 1.8 mg reduced HbA1c by 1.3% with mean weight loss of 1.8 kg 4

When to use insulin instead of GLP-1 receptor agonists:

• Extreme symptomatic hyperglycemia with glucose >300 mg/dL 1
• Evidence of ongoing catabolism or ketonuria suggesting profound insulin deficiency 1
• Cost or tolerability issues with GLP-1 receptor agonists 1

Insulin Initiation When Required

If insulin becomes necessary:

• Basal insulin is preferred over premixed or prandial insulin when starting insulin therapy, as it has less hypoglycemia and weight gain 1
• Long-acting analogs (glargine, detemir) have modestly less overnight hypoglycemia than NPH insulin 1
• Initiate basal insulin at 10 units daily or 0.1-0.2 units/kg/day 1
• Titrate based on fasting glucose, increasing by 2 units every 3 days until fasting glucose reaches target 1
• Consider GLP-1 receptor agonist/basal insulin combination for complementary outcomes: greater efficacy, weight benefit, and reduced hypoglycemia compared to insulin intensification alone 1

Intensification Beyond Basal Insulin

If glycemic targets are not met on basal insulin plus oral agents:

• Add GLP-1 receptor agonist, SGLT2 inhibitor, or prandial insulin 1
• GLP-1 receptor agonists are preferred over prandial insulin intensification due to weight and hypoglycemia advantages 1
• If prandial insulin is needed, start with 4 units at the largest meal or meal with greatest postprandial glucose excursion 1
• Increase prandial insulin by 1-2 units or 10-15% twice weekly based on postprandial glucose 1

Hypertension Management

For hypertension management in patients with diabetes:

• Target blood pressure should generally be <140/90 mmHg, with <130/80 mmHg for patients at higher cardiovascular risk
• ACE inhibitors or ARBs are preferred first-line agents in diabetic patients due to renal protective effects
• Thiazide diuretics or calcium channel blockers are appropriate second-line additions
• Beta-blockers should be reserved for specific indications (post-MI, heart failure) as they may mask hypoglycemia symptoms

Hypothyroidism Management

For hypothyroidism:

• Levothyroxine is the standard treatment, initiated at 1.6 mcg/kg/day in most adults
• Start at lower doses (25-50 mcg daily) in elderly patients or those with cardiac disease
• Monitor TSH 6-8 weeks after initiation and after any dose adjustment
• Target TSH 0.5-2.5 mIU/L for most patients
• Take levothyroxine on empty stomach, 30-60 minutes before breakfast, separate from other medications

Critical Drug Interactions and Monitoring

Important considerations when managing all three conditions:

• Metformin is contraindicated in severe renal impairment; monitor renal function regularly 1
• When combining sulfonylureas with GLP-1 receptor agonists or insulin, reduce sulfonylurea dose by 50% to minimize hypoglycemia risk 3
• DPP-4 inhibitors increase hypoglycemia risk by approximately 50% when added to sulfonylureas 3
• Review all medications regularly; stop or reduce doses if minimal benefit or harm outweighs benefit 1
• When HbA1c falls below 6.5% or substantially below individualized target, reduce or stop medications with hypoglycemia or weight gain risk 1