Drug Treatment of Diabetes Mellitus

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Classification			Members	Adult Dose	Pediatric Dose	Renal Dosing	Mechanism of Action	Side Effects
α-Glucosidase Inhibitors					Acarbose	25 mg three times daily before meals, titrated up to 100 mg three times daily	Indication: Type 2 diabetes, used as adjunct therapy to diet and exercise. Initial dose: 25 mg three times a day with meals for children ≥ 10 years old. Titration: Increase by 25 mg every 1–2 weeks based on clinical response. Maximum dose: 100 mg three times a day	No dose adjustment needed	slow the breakdown of starches in the intestines, which helps prevent blood sugar spikes after meals	Gastrointestinal issues: Gas, bloating, and diarrhea. Liver enzyme abnormalities: Rare but possible
α-Glucosidase Inhibitors						Meglitol
Insulin Sensitizers	Biguanides			Metformin	Initial dose: 500 mg BID or 850 mg once daily. Maintenance dose: 500 mg to 2000 mg daily, in divided doses	Indication: Type 2 diabetes (usually in combination with diet and exercise) Initial dose: 500 mg once or twice daily Titration: Increase by 500 mg weekly (or every 2 weeks) to minimize gastrointestinal side effects. Maximum dose: 2000–2500 mg/day (based on tolerance and clinical judgment). Notes: Doses greater than 2000 mg/day may be used in older children (16+), but safety and efficacy beyond this dose are not well-established in younger children.	CrCl > 60 mL/min: No dose adjustment needed. CrCl 45-59 mL/min: No dose adjustment needed. CrCl 30-44 mL/min: Reduce dose to half. CrCl < 30 mL/min: Metformin is generally contraindicated due to the risk of lactic acidosis.	This is often the first-line treatment for type 2 diabetes. It works by reducing the amount of glucose produced by the liver and improving the body's response to insulin	Gastrointestinal issues: Nausea, diarrhea, stomach pain, and bloating. Vitamin B12 deficiency: Long-term use may lead to lower levels of vitamin B12
		Thiazolidinediones (Glitazones)			Pioglitazone	15-30 mg daily	Indication: Type 2 diabetes (used infrequently in children). Dose: Not widely used in pediatrics; however, a typical adult dose of pioglitazone is 15–45 mg/day, adjusted based on clinical judgment and patient tolerance. Caution: There is limited pediatric data on the safety and long-term use of thiazolidinediones.	No dose adjustment needed	Improve insulin sensitivity in muscle and fat cells. They can cause weight gain and fluid retention.	Weight gain: Can cause significant weight gain. Fluid retention: Leading to swelling and an increased risk of heart failure. Bone fractures: Higher risk of fractures, particularly in women
		Thiazolidinediones (Glitazones)				Rosiglitazone		4-8 mg daily				Use with caution
Insulin Secretagogues	Sulfonylureas	First Generation	Acetohexamide				Stimulate the pancreas to produce more insulin	Hypoglycemia: Low blood sugar levels can occur, especially if meals are skipped. Weight gain: These medications can lead to an increase in weight. Skin reactions: Rashes or itching may occur
						Carbutamide
						Chlorpropamide					CrCl < 50 mL/min: Avoid use
						Glycyclamide
						Metahexamide
						Tolbutamide
						Tolazamide
				Second Generation	Glibizide	5 mg daily, titrated up to 40 mg daily			Initial dose: 2.5–5 mg/day for children ≥ 10 years old. Titration: Increase by 2.5–5 mg every 1–2 weeks based on clinical response. Maximum dose: 20 mg/day (typically lower doses are used in pediatric patients)	CrCl > 60 mL/min: No dose adjustment needed. CrCl 30-59 mL/min: Reduce dose by 50% CrCl < 30 mL/min: Use with caution; consider switching to insulin
						Glibornuride
						Gliclazide					Mild renal impairment (creatinine clearance >30 mL/min): The usual dose can be used with caution. Severe renal impairment: Should be avoided, or dose reduced.
						Gliquidone
						Glisoxebide
						Glyburide (Glibenclamide)			1.25-5 mg daily, titrated up to 20 mg daily	Not recommended	CrCl > 60 mL/min: No dose adjustment needed. CrCl 30-59 mL/min: Reduce dose by 50% CrCl < 30 mL/min: Glyburide is generally avoided due to the risk of prolonged hypoglycemia
				Third Generation	Glimepiride				Initial dose: 1–2 mg/day for children ≥ 10 years old. Titration: Increase every 1–2 weeks based on blood glucose response. Maximum dose: 4 mg/day	CrCl > 60 mL/min: No dose adjustment needed CrCl 30-59 mL/min: Reduce dose by 50% CrCl < 30 mL/min: Use with caution; consider switching to insulin
		Meglitinides			Repaglinide	0.5 mg before each meal, titrated up to 4 mg before each meal		CrCl > 60 mL/min: No dose adjustment needed. CrCl 30-59 mL/min: Reduce dose by 50%. CrCl < 30 mL/min: Use with caution; consider switching to insulin	Similar to sulfonylureas, these drugs, stimulate insulin release but are taken with meals to reduce the risk of hypoglycemia	Hypoglycemia: Similar to sulfonylureas, these can cause low blood sugar levels. Weight gain: Less common but can occur
						Mitiglinide
						Nateglinide	60 mg before each meal, titrated up to 120 mg before each meal				CrCl > 60 mL/min: No dose adjustment needed CrCl 30-59 mL/min: Reduce dose by 50% CrCl < 30 mL/min: Use with caution; consider switching to insulin
SGLT2 Inhibitors (Gliflozins)					Canagliflozin	100 mg daily	not approved for use in children under 18, but may be considered under specialized care in some cases, based on adult data	CrCl < 45 mL/min: Use with caution. Canagliflozin and dapagliflozin are not recommended for initiation at CrCl < 45 mL/min	work by preventing the kidneys from reabsorbing glucose, leading to its excretion in urine	Yeast infections: Both genital and urinary tract yeast infections. Dehydration: Leading to dizziness or low blood pressure. Ketoacidosis: A rare but serious condition with high blood ketone levels. Lower limb amputations: Increased risk, particularly with canagliflozin
						Empagliflozin					Approved for children aged 10-18 years. The dose is typically 2.5-10 mg daily, depending on the child's needs and response to treatment
						Dapagliflozin	5 mg daily, titrated up to 10 mg daily
						Ertugliflozin
Incretin Mimetics (Peptide Analogs) DPP4-Inhibitors (GLIPTINS)					Alogliptin				mimic the action of incretin hormones, which increase insulin release and decrease glucagon levels	Upper respiratory tract infections: Symptoms like a runny nose and sore throat. Joint pain: Some people may experience joint pain. Pancreatitis: Rare but serious inflammation of the pancreas.
						Anagliptin
						Linagliptin
						Saxagliptin	2.5-5 mg daily				2.5 mg daily for CrCl 30-59 mL/min; avoid use if CrCl < 15 mL/min.
						Sitagliptin	100 mg daily	Indication: Type 2 diabetes in children ≥10 years old. Initial dose: 100 mg once daily. Notes: Doses may need adjustment in children with renal impairment			50 mg daily for CrCl 30-59 mL/min; 25 mg daily for CrCl 15-29 mL/min
						Tenegliptin

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Drug Treatment of Diabetes Mellitus

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