Schedule H

Subcutaneous Injection

• Prefilled Pen Injection: 6 mg/mL (3 mL pen delivering 18 mg total per pen)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Type 2 Diabetes Mellitus

As adjunct to diet and exercise; may be used as monotherapy (when metformin is contraindicated/not tolerated) or in combination with oral antidiabetic agents and/or basal insulin. Particularly beneficial in overweight/obese patients.

Parameter Recommendation

Starting dose 0.6 mg subcutaneously once daily for at least 1 week

Titration Increase to 1.2 mg once daily after ≥1 week; may further increase to 1.8 mg once daily after ≥1 additional week if needed

Usual maintenance dose 1.2–1.8 mg subcutaneously once daily

Maximum dose 1.8 mg once daily

Clinical Notes:

• Administer at any time of day, independent of meals (same time each day preferred)

• Initial 0.6 mg dose is for GI tolerability; not therapeutically effective

• May be injected in abdomen, thigh, or upper arm; rotate injection sites

• Continue metformin unless contraindicated

• When adding to sulfonylurea or insulin, consider dose reduction of these agents to minimise hypoglycaemia risk

1. Chronic Weight Management (Obesity)

For adults with BMI ≥30 kg/m² (obese) or BMI ≥27 kg/m² (overweight) with at least one weight-related comorbidity (e.g., T2DM, hypertension, dyslipidaemia). Available as Saxenda® brand.

Parameter Recommendation

Starting dose 0.6 mg subcutaneously once daily for 1 week

Titration Increase by 0.6 mg weekly increments (0.6 → 1.2 → 1.8 → 2.4 → 3.0 mg)

Usual maintenance dose 3.0 mg subcutaneously once daily (achieved after 5 weeks of titration)

Maximum dose 3.0 mg once daily

Clinical Notes:

• If patient cannot tolerate dose escalation to 3.0 mg, discontinue therapy

• Evaluate response at 16 weeks on 3.0 mg dose; discontinue if <5% weight loss achieved

• Must be used alongside reduced-calorie diet and increased physical activity

• Not indicated solely for cosmetic weight loss

Secondary Indications – Adults (Off-label, if any)

Indication Dose Duration Notes

Cardiovascular Risk Reduction in T2DM with Established CVD 1.8 mg SC once daily Long-term OFF-LABEL in India; Specialist only; Evidence: LEADER trial demonstrated CV mortality benefit; Not yet incorporated in ICMR guidelines

Non-Alcoholic Fatty Liver Disease (NAFLD/NASH) in T2DM with Obesity 1.2–1.8 mg SC once daily Long-term OFF-LABEL; Specialist only; Emerging evidence from international RCTs; Limited Indian data

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Type 2 Diabetes Mellitus in Children ≥10 Years

Parameter Recommendation

Starting dose 0.6 mg subcutaneously once daily for at least 1 week

Titration Increase by 0.6 mg weekly based on glycaemic response and tolerability

Usual maintenance dose 1.2–1.8 mg subcutaneously once daily

Maximum dose 1.8 mg once daily

Clinical Notes:

• Minimum age: 10 years

• Use only under paediatric endocrinology specialist supervision

• Monitor for GI intolerance (nausea, vomiting) during dose escalation

• Assess growth parameters, HbA1c, and blood glucose regularly

• Continue lifestyle modifications alongside pharmacotherapy

Secondary Indications – Paediatrics (Off-label, if any)

Indication Age Dose Notes

Obesity in Adolescents ≥12 years Starting: 0.6 mg daily; Titrate by 0.6 mg weekly to 3.0 mg daily OFF-LABEL in India; Specialist only (Paediatric Endocrinology); Evidence: SCALE Teens trial; Very limited Indian experience

Not recommended below age 10 years for T2DM or below age 12 years for obesity except under specialist supervision in tertiary centres.

Note: Liraglutide is not renally eliminated; however, dehydration from GI adverse effects may precipitate renal impairment. Ensure adequate hydration.

• Personal or family history of medullary thyroid carcinoma (MTC)

• Multiple endocrine neoplasia syndrome type 2 (MEN 2)

• Known hypersensitivity to liraglutide or any excipient

• Pregnancy (for weight management indication — contraindicated)

• History of serious hypersensitivity reactions to GLP-1 receptor agonists

• History of pancreatitis — increased risk; discontinue immediately if pancreatitis suspected

• Gallbladder disease — increased incidence of cholelithiasis and cholecystitis reported

• Severe gastrointestinal disease (e.g., gastroparesis, inflammatory bowel disease) — may exacerbate symptoms

• Dehydration risk — due to nausea, vomiting, diarrhoea; ensure adequate fluid intake

• Concurrent use with insulin or sulfonylureas — increased hypoglycaemia risk; consider dose reduction of insulin/sulfonylurea

• Thyroid nodules or goitre — monitor; refer for evaluation if symptomatic

• History of suicidal ideation or depression — monitor closely (particularly in weight management use)

• Diabetic retinopathy — rapid improvement in glycaemic control may transiently worsen retinopathy

Parameter Details

Risk Category Not recommended during pregnancy

Known Risks Animal studies suggest potential effects on fetal growth; limited human data

Weight Management Indication Contraindicated — discontinue at least 2 months before planned conception

Diabetes Indication Avoid; use only if potential benefit clearly outweighs risk and no safer alternative available

Preferred Alternatives Insulin is the preferred antidiabetic in pregnancy; Metformin may be continued in selected cases (ICMR, FOGSI guidelines)

Monitoring If inadvertently exposed, discontinue immediately; monitor fetal growth; obstetric referral

Parameter Details

Compatibility Not recommended during breastfeeding

Drug Levels in Milk Unknown in humans; animal studies show low levels in milk

Preferred Alternatives Insulin or metformin (better characterised safety during lactation)

Infant Monitoring If inadvertent exposure, monitor infant for feeding difficulties, GI symptoms, and adequate weight gain

Parameter Recommendation

Starting dose 0.6 mg subcutaneously once daily (same as adults)

Titration Slower escalation recommended; allow 2 weeks at each dose level if GI intolerance

Special Risks Increased risk of dehydration, hypovolaemia, falls (due to dizziness/nausea); age-related decline in renal function; weight loss may be excessive in frail elderly

Monitoring Renal function, hydration status, nutritional status, signs of dehydration

Age ≥75 years Very limited experience; use with caution; avoid in frail elderly

Interacting Drug Mechanism / Effect Recommendation

Insulin Additive hypoglycaemia risk Reduce insulin dose by 10–20% when initiating liraglutide; monitor blood glucose closely

Sulfonylureas (glimepiride, gliclazide, glibenclamide) Additive hypoglycaemia risk Consider reducing sulfonylurea dose when initiating liraglutide

Warfarin Delayed gastric emptying may alter warfarin absorption Monitor INR closely during initiation and dose changes

Oral Contraceptives Delayed gastric emptying may reduce absorption; severe vomiting may impair efficacy Consider backup contraception during initial weeks or if significant vomiting occurs

Interacting Drug Mechanism / Effect Recommendation

Digoxin Delayed gastric emptying may alter digoxin absorption kinetics Monitor digoxin levels and clinical response

Levothyroxine Delayed gastric emptying may affect absorption Monitor TSH; may need timing adjustment

Paracetamol / Other oral medications Delayed gastric emptying may slow absorption and reduce peak concentrations Generally not clinically significant; monitor efficacy of time-sensitive medications

Pioglitazone Additive fluid retention possible Use with caution in patients with heart failure or oedema

ACE Inhibitors / ARBs Combined with dehydration from GI effects may increase AKI risk Ensure adequate hydration; monitor renal function

• Nausea (very common; especially during initiation and titration)

• Vomiting

• Diarrhoea

• Constipation

• Abdominal pain/discomfort

• Dyspepsia

• Decreased appetite

• Headache

• Dizziness

• Fatigue

• Injection site reactions (erythema, pain, pruritus)

• Hypoglycaemia (when combined with insulin/sulfonylureas)

Adverse Effect Clinical Action

Acute Pancreatitis Discontinue permanently; hospitalisation; supportive care; do not rechallenge

Gallbladder Disease (cholelithiasis, cholecystitis) Evaluate promptly; surgical consultation if symptomatic; may require discontinuation

Acute Kidney Injury Usually secondary to dehydration from severe GI effects; discontinue temporarily; rehydration; monitor renal function

Medullary Thyroid Carcinoma (theoretical risk) Counsel patients about thyroid tumour symptoms (neck mass, dysphagia, dyspnoea, hoarseness); investigate promptly if symptoms develop

Severe Hypersensitivity Reactions (angioedema, anaphylaxis) Discontinue permanently; supportive care

Suicidal Ideation / Psychiatric Symptoms (rare; mainly in weight management use) Discontinue; psychiatric evaluation and support

Worsening of Diabetic Retinopathy Ophthalmology referral; continue glycaemic management with close monitoring

First 4–8 weeks GI tolerability assessment; blood glucose monitoring; symptoms of dehydration; hypoglycaemia (if on insulin/sulfonylureas)

Every 3 months HbA1c, weight, BMI

Every 6–12 months Renal function, hepatic function, thyroid examination

Ongoing Symptoms suggestive of pancreatitis (severe abdominal pain), gallbladder disease, or thyroid nodules; mental health monitoring (weight management indication)

Note: Lipase/amylase testing only if symptoms suggestive of pancreatitis; routine measurement not recommended.

For Type 2 Diabetes (1.2–1.8 mg dosing):

• Victoza (Novo Nordisk) — 6 mg/mL, 3 mL prefilled pen

For Weight Management (3.0 mg dosing):

• Saxenda (Novo Nordisk) — 6 mg/mL, 3 mL prefilled pen

Note: Victoza and Saxenda are NOT interchangeable — different approved indications and dosing regimens.

Product Approximate Price per Pen

• Not included in NLEM; pricing not NPPA-controlled

• High cost limits accessibility; insurance coverage variable

• Government supply availability very limited

• Each pen provides multiple doses depending on prescribed daily dose

• Always initiate at 0.6 mg/day regardless of indication — this is for GI tolerability, not therapeutic effect; do not skip this step

• Nausea is the most common reason for discontinuation — counsel patients that it typically improves over 4–8 weeks; recommend smaller, frequent meals

• Ideal agent for obese/overweight T2DM patients as it provides glycaemic control with weight loss benefit (typically 2–5 kg)

• When adding to insulin or sulfonylurea, proactively reduce the dose of these agents to prevent hypoglycaemia

• Do NOT interchange Victoza (diabetes) and Saxenda (obesity) — they have different dosing, indications, and regulatory approvals

• Discontinue if <5% weight loss after 16 weeks at 3.0 mg/day (obesity indication) — non-responders unlikely to benefit from continued therapy

• Avoid in patients with personal or family history of MTC or MEN 2 — black box warning for thyroid C-cell tumours in rodent studies

• "Sick day rules": Advise patients to ensure adequate hydration during GI illness; temporary discontinuation may be needed

Liraglutide; type 2 diabetes; obesity; GLP-1 receptor agonist; injectable antidiabetic; weight loss; cardiovascular benefit; pancreatitis risk; MTC contraindication; pregnancy-avoid; renal-caution; Schedule H

RxIndia v1.0 — 20 Apr 2025

• CDSCO approved product information (Victoza, Saxenda)

• Indian Pharmacopoeia (IP)

• API Textbook of Medicine — Diabetes Mellitus and Obesity chapters

• ICMR Guidelines for Management of Type 2 Diabetes (2018)

• AIIMS Endocrinology Treatment Protocols

• Harrison's Principles of Internal Medicine

• Goodman & Gilman's: The Pharmacological Basis of Therapeutics

• LEADER Trial (for off-label cardiovascular indication reference)

• SCALE Trials (for off-label paediatric obesity reference)