Generic Name

Janumet

Mechanism

• *Sitagliptin*
• Inhibits dipeptidyl‑peptidase‑4 (DPP‑4), preventing degradation of incretin hormones GLP‑1 and GIP.
• Increases insulin secretion and suppresses glucagon release in a glucose‑dependent manner, leading to improved post‑prandial glucose control.
• *Metformin*
• Decreases hepatic gluconeogenesis and improves insulin sensitivity in peripheral tissues.
• Enhances GLUT‑4 translocation, increasing glucose uptake by adipose and muscle cells.
• Reduces intestinal glucose absorption.

Combined, they provide complementary mechanisms that lower fasting and post‑prandial glucose levels while minimizing hypoglycaemia risk.

Pharmacokinetics

Renal function drastically affects Sitagliptin clearance; dose adjustment is required for CrCl < 30 mL/min. Metformin is contraindicated for CrCl < 30 mL/min due to lactic acidosis risk.

Indications

• Management of type 2 diabetes mellitus in adults.
• Used add‑on to diet, exercise, and/or metformin monotherapy.
• Can also be added to other oral antidiabetic agents (e.g., sulfonylureas, thiazolidinediones) if tolerated.
• Not approved for type 1 diabetes or diabetic ketoacidosis.

Contraindications

• Contraindicated in patients with:
• Renal impairment (CrCl < 30 mL/min).
• Pregnancy and lactation.
• Significant hepatic dysfunction (Cirrhosis, chronic hepatitis).
• Warnings:
• Lactic acidosis: rare but serious; avoid in patients with renal failure, metformin-associated lactic acidosis risk.
• Hypoglycaemia: minimal risk with Sitagliptin alone; risk increases if combined with insulin or sulfonylureas.
• Pancreatitis: rare, monitor symptoms.

Dosing

• Titration:

1. Start at 50/500 mg once daily.

2. After 4 weeks, increase to 100/500 mg if glycaemic targets not met.

3. For renal function decline, hold or reduce dose per CrCl category.
• Administration: Swallow whole; optional in water. Not crushable or chewable.
• Missed dose: Take as soon as remembered; skip if next dose within 12 h.

Adverse Effects

Common (≥ 1 % frequency)
• Gastrointestinal: nausea, diarrhoea, vomiting, abdominal cramps
• Upper respiratory infections
• Headache

Serious (rare)
• Lactic acidosis (symptoms: muscle pain, fatigue, abdominal pain, dyspnea)
• Renal impairment exacerbation
• Hypoglycaemia (especially with insulin or sulfonylureas)
• Pancreatitis (abdominal pain, nausea)
• Hypersensitivity reactions (rash, angioedema)

Monitoring

Clinical Pearls

• Low hypoglycaemia risk: Sitagliptin’s glucose‑dependent action makes it safer to combine with Metformin without increasing hypoglycaemia, unless additional insulinogenic agents are used.
• Weight neutral: Unlike sulfonylureas or insulin, Janumet neither promotes nor causes significant weight gain, ideal for cardio‑metabolic risk management.
• Renal-based dosing: Sitagliptin requires dose adjustment for CrCl 30–60 mL/min, but Metformin’s safety threshold is more stringent (< 30 mL/min); keep both drugs under close renal surveillance.
• Lactic acidosis vigilance: Although rare (< 1 /10,000), patients with renal or hepatic compromise should be screened for symptoms before initiating Metformin.
• Pancreatitis risk: While evidence is limited, patient education on abdominal pain and prompt evaluation can mitigate severe outcomes.
• Administration timing: Taken once daily, food does not affect absorption, but aligning dosing with the first meal can reduce GI discomfort.

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• Key pharmacology terms: *DPP‑4 inhibitor, GLP‑1, Metformin, hepatic gluconeogenesis, insulin sensitivity, hypoglycaemia, lactic acidosis, creatinine clearance, HbA1c.*

These concise yet comprehensive points should serve medical students and practice‑based clinicians as a quick reference for Janumet’s pharmacodynamic profile, clinical use, safety, and monitoring.