What are the current pharmacologic agents used to treat diabetes mellitus and their typical dosing ranges?

Current Diabetes Medications and Typical Dosing Ranges

Insulin Therapy

Basal (Long-Acting) Insulins

• Insulin glargine (Lantus, Basaglar, Toujeo) and insulin detemir (Levemir) are preferred over NPH insulin because they deliver a flatter, more constant plasma profile and reduce hypoglycemia risk 1.
• Insulin degludec (Tresiba) offers once-daily dosing with an ultra-long duration of action 2.
• Initial dosing for type 2 diabetes: Start with 10 units once daily or 0.1–0.2 units/kg body weight, administered at the same time each day 2.
• Initial dosing for type 1 diabetes: Total daily insulin requirement is typically 0.4–1.0 units/kg/day, with approximately 40–50% given as basal insulin 2, 1.
• Titration: Increase by 2 units every 3 days if fasting glucose is 140–179 mg/dL; increase by 4 units every 3 days if fasting glucose ≥180 mg/dL, targeting 80–130 mg/dL 2.
• Critical threshold: When basal insulin exceeds 0.5 units/kg/day without achieving targets, add prandial insulin rather than continuing basal escalation to avoid "over-basalization" 2.

Prandial (Rapid-Acting) Insulins

• Insulin lispro (Humalog), insulin aspart (NovoLog, Fiasp), and insulin glulisine (Apidra) are recommended over regular human insulin due to faster onset, higher peak, and shorter duration that better matches meal glucose spikes 1, 3, 4.
• Timing: Administer 0–15 minutes before meals (ideally immediately before eating) for optimal postprandial control 2, 1.
• Initial dosing: Start with 4 units before the largest meal or 10% of the current basal dose 2.
• Titration: Increase each meal dose by 1–2 units (≈10–15%) every 3 days based on 2-hour postprandial glucose, targeting <180 mg/dL 2.
• Clinical benefit: Rapid-acting analogs reduce postprandial hyperglycemia and decrease hypoglycemia frequency by approximately 12% compared to regular human insulin 3.

Premixed Insulins

• 70/30 insulin (70% NPH/30% regular) and 75/25 or 50/50 insulin analogue mixtures may be used but are not recommended for hospitalized patients due to a 64% hypoglycemia rate versus 24% with basal-bolus therapy 2.
• Two or three premixed insulin injections per day may be used in type 1 diabetes, though basal-bolus regimens are preferred 5.

Oral Antidiabetic Medications

Biguanides

• Metformin is the foundation of type 2 diabetes therapy and should be continued at maximum tolerated dose (up to 2,000–2,550 mg daily) when adding insulin, as it reduces total insulin requirements by 20–30% 2.
• Dosing: Start 500 mg once or twice daily with meals; titrate up to 1,000 mg twice daily (2,000 mg total) as tolerated 2.
• Renal adjustment: Continue if eGFR ≥60 mL/min/1.73 m²; reduce to maximum 1,000 mg/day if eGFR 30–44 mL/min/1.73 m²; discontinue if eGFR <30 mL/min/1.73 m² 6.

SGLT2 Inhibitors

• Dapagliflozin (Farxiga), empagliflozin (Jardiance), and canagliflozin (Invokana) provide cardiovascular and renal protection independent of glycemic control 6.
• Dapagliflozin dosing: 10 mg once daily for cardiovascular/renal protection if eGFR ≥25 mL/min/1.73 m²; for glycemic control, start 5 mg once daily if eGFR ≥45 mL/min/1.73 m², may increase to 10 mg 6.
• Clinical benefits: Dapagliflozin reduces kidney disease progression by 44%, cardiovascular death or heart failure hospitalization by 29%, and all-cause mortality by 31% 6.
• Safety: Withhold at least 3 days before major surgery; temporarily discontinue during acute illness with reduced oral intake, fever, vomiting, or diarrhea 6.

DPP-4 Inhibitors

• Sitagliptin (Januvia) 100 mg once daily (standard dose); reduce to 50 mg once daily if eGFR 30–44 mL/min/1.73 m² 6.
• Linagliptin (Tradjenta) 5 mg once daily requires no dose adjustment regardless of renal function 6.
• Efficacy: DPP-4 inhibitors provide an additional 0.5–0.8% HbA1c reduction when added to metformin 6.

Sulfonylureas

• Gliclazide and glipizide provide no cardiovascular or renal protection and increase hypoglycemia risk, especially in CKD 6.
• Recommendation: Discontinue sulfonylureas when initiating basal-bolus insulin to avoid additive hypoglycemia risk 2.

Injectable Non-Insulin Medications

GLP-1 Receptor Agonists

• Semaglutide (Ozempic, Wegovy), liraglutide (Victoza), and dulaglutide (Trulicity) provide cardiovascular protection and can be used across all stages of CKD without dose adjustment 6.
• Semaglutide dosing: Start 0.25 mg subcutaneously once weekly for 4 weeks, then increase to 0.5 mg weekly; may increase to 1 mg weekly after at least 4 weeks if additional glycemic control needed 6.
• Clinical benefit: GLP-1 receptor agonists reduce new or worsening nephropathy by 36% and provide comparable or better HbA1c reduction than prandial insulin with lower hypoglycemia risk and weight loss 6.
• Combination with insulin: When adding GLP-1 RA to basal insulin, reduce basal insulin dose by approximately 20% to avoid hypoglycemia 6.

Key Clinical Algorithms

Type 1 Diabetes Initial Regimen

• Total daily dose: 0.5 units/kg/day for metabolically stable patients (range 0.4–1.0 units/kg/day) 2, 1.
• Distribution: 40–50% as basal insulin once daily; 50–60% as prandial insulin divided among three meals 2, 1.
• Example for 70 kg patient: Total 35 units/day → 17.5 units basal (e.g., glargine at bedtime) + 17.5 units prandial (≈6 units before each meal) 2.

Type 2 Diabetes Insulin Initiation

• Step 1: Start basal insulin 10 units once daily or 0.1–0.2 units/kg/day while continuing metformin 2.
• Step 2: Titrate basal insulin every 3 days until fasting glucose 80–130 mg/dL 2.
• Step 3: If HbA1c remains above target after 3–6 months despite fasting glucose at goal, add prandial insulin 4 units before largest meal 2.
• Step 4: Titrate prandial insulin by 1–2 units every 3 days based on 2-hour postprandial glucose 2.

Hospitalized Patient Basal-Bolus Regimen

• Initial dose: 0.3–0.5 units/kg/day total (50% basal, 50% prandial divided among three meals) 2.
• High-risk patients (age >65, renal impairment, poor intake): Start 0.1–0.25 units/kg/day 2.
• Correction insulin: Add 2 units for pre-meal glucose >250 mg/dL; add 4 units for >350 mg/dL 2.
• Monitoring: Check glucose before each meal and at bedtime (minimum 4 times daily) 2.

Sliding-Scale Insulin Is Condemned

• Major diabetes guidelines explicitly condemn sliding-scale insulin as monotherapy because it reacts to hyperglycemia rather than preventing it, achieving mean glucose <140 mg/dL in only ≈38% of patients versus ≈68% with scheduled basal-bolus therapy 2.
• Correction doses must supplement—not replace—scheduled basal and prandial insulin 2.