Schedule H

Subcutaneous

• Pre-filled injection pen: 0.75 mg/0.5 mL

• Pre-filled injection pen: 1.5 mg/0.5 mL

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indication: Type 2 Diabetes Mellitus (Adults)

As monotherapy or in combination with other antidiabetic agents (oral agents or basal insulin)

Parameter Recommendation

Starting dose 0.75 mg subcutaneously once weekly

Titration May increase to 1.5 mg once weekly after ≥4 weeks if additional glycaemic control is required

Usual maintenance dose 0.75–1.5 mg subcutaneously once weekly

Maximum dose 1.5 mg subcutaneously once weekly

Clinical Notes:

• Administer once weekly on the same day each week, at any time of day, with or without meals

• Inject subcutaneously in abdomen, thigh, or upper arm; rotate injection sites

• If a dose is missed, administer as soon as remembered if within 3 days; otherwise, skip and resume on next scheduled day

• When adding to existing sulfonylurea or insulin therapy, consider reducing sulfonylurea/insulin dose to minimise hypoglycaemia risk

• Not indicated for type 1 diabetes mellitus or diabetic ketoacidosis

Secondary Indications — Adults (Off-label)

Indication Dose Notes

Weight management in T2DM with obesity 1.5 mg SC once weekly OFF-LABEL • Specialist only • Duration based on clinical response and tolerability • Evidence: Post-hoc analyses from AWARD trials and international data suggest modest weight reduction benefit (~2–3 kg) • Not a primary indication for weight loss in India

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Not approved for paediatric use in India.

Secondary Indications — Paediatrics (Off-label)

Not applicable.

Age Restriction:

• Not recommended below 18 years of age due to lack of safety and efficacy data in paediatric population in India

Note: Gastrointestinal adverse effects (nausea, vomiting, diarrhoea) may lead to dehydration, potentially worsening renal function; monitor fluid status closely.

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

• Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)

• Known hypersensitivity to dulaglutide or any component of the formulation

• History of serious hypersensitivity reaction to any GLP-1 receptor agonist

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

• Severe gastrointestinal disease including gastroparesis — may exacerbate symptoms

• Pre-existing diabetic retinopathy — rapid improvement in glycaemic control may transiently worsen retinopathy; monitor closely

• Risk of dehydration from persistent nausea, vomiting, or diarrhoea — especially in elderly or those with renal impairment

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

• Rapid dose escalation — increases gastrointestinal intolerance

Parameter Details

Overall safety Not recommended — insufficient human data; animal studies show fetal growth reduction and skeletal abnormalities

Preferred alternatives Insulin is the standard of care for diabetes management in pregnancy in India

When it may be used Only if no suitable alternative and benefit clearly outweighs risk — specialist endocrinologist decision

What to monitor Maternal blood glucose closely; fetal growth and development; discontinue at least 2 months before planned conception

Parameter Details

Compatibility Not recommended during breastfeeding

Preferred alternatives Insulin (does not enter breast milk in significant amounts)

Expected drug levels in milk Unknown — excretion in human milk not established

What to monitor in infant Feeding difficulties, poor weight gain, gastrointestinal symptoms if exposure occurs

Parameter Recommendation

Starting dose 0.75 mg subcutaneously once weekly

Titration Cautious titration; assess gastrointestinal tolerance and renal function before dose escalation

Additional risks Higher susceptibility to gastrointestinal adverse effects; increased dehydration risk; monitor renal function as GI effects may precipitate acute kidney injury; avoid in frail elderly with poor oral intake

Interacting Drug Effect Mechanism / Management

Sulfonylureas Increased hypoglycaemia risk Consider reducing sulfonylurea dose by 50% when initiating dulaglutide

Insulin Increased hypoglycaemia risk Consider reducing basal insulin dose by 10–20% when initiating dulaglutide; titrate based on glucose monitoring

Oral medications with narrow therapeutic index (e.g., Warfarin, Digoxin) Delayed gastric emptying may affect absorption and time to peak concentration Monitor INR more frequently when initiating warfarin combination; monitor digoxin levels and clinical response

Interacting Drug Effect Management

Other GLP-1 receptor agonists (e.g., Liraglutide, Semaglutide) Pharmacological duplication; no added benefit Avoid concurrent use

DPP-4 inhibitors (e.g., Sitagliptin, Vildagliptin) Overlapping mechanism (incretin-based); no additional efficacy Avoid combination — discontinue DPP-4 inhibitor when starting dulaglutide

Oral contraceptives Delayed gastric emptying may theoretically affect absorption Clinical significance uncertain; advise barrier method if gastrointestinal symptoms are significant

Paracetamol, Antibiotics Delayed absorption possible Monitor clinical effect; usually not clinically significant

• Nausea (most common; typically decreases over time)

• Diarrhoea

• Vomiting

• Abdominal pain / discomfort

• Decreased appetite

• Dyspepsia

• Fatigue

• Injection site reactions

Adverse Effect Notes

Acute pancreatitis Discontinue immediately if suspected; do not rechallenge; presents with persistent severe abdominal pain

Severe hypersensitivity reactions / Anaphylaxis Discontinue permanently; includes angioedema, urticaria, anaphylaxis

Medullary thyroid carcinoma (MTC) Theoretical risk from rodent studies; clinical significance in humans uncertain; avoid in those with personal/family history of MTC or MEN 2

Acute kidney injury Secondary to dehydration from severe gastrointestinal adverse effects; monitor renal function

Worsening of diabetic retinopathy Rare; monitor in patients with pre-existing retinopathy during rapid glycaemic improvement

Phase Parameters

Baseline Fasting blood glucose, HbA1c, renal function (serum creatinine, eGFR), hepatic function, thyroid history (personal and family), history of pancreatitis, fundoscopy in patients with retinopathy

Initiation / Titration Gastrointestinal tolerance assessment; blood glucose monitoring; signs and symptoms of pancreatitis; hydration status

Long-term HbA1c every 3 months initially, then every 6 months when stable; weight; renal function annually or more frequently if GI symptoms persist; periodic retinal examination in at-risk patients

• Trulicity (Eli Lilly) — 0.75 mg/0.5 mL and 1.5 mg/0.5 mL pre-filled pens

Note: Not included in NLEM 2022; not under NPPA price control. High cost limits accessibility for many patients.

1. Managing GI adverse effects: Initiate at 0.75 mg to minimise nausea; advise patients that nausea typically improves after 2–4 weeks; recommend smaller, more frequent meals during initiation phase

1. Once-weekly convenience: Excellent option for patients with adherence challenges to daily medications; advise setting a weekly reminder; same day each week preferred but can be changed if needed

1. Cardiovascular benefit: REWIND trial demonstrated reduction in major adverse cardiovascular events (MACE) in T2DM patients with and without established CVD — consider for T2DM patients with high cardiovascular risk

1. Weight effect: Modest weight loss (~2–3 kg) typically observed; not a primary weight loss agent but beneficial in overweight/obese T2DM patients

1. Avoid with DPP-4 inhibitors: Discontinue DPP-4 inhibitors when initiating dulaglutide — overlapping mechanism with no additional glycaemic benefit

1. Injection technique: Pre-filled single-use pen; no reconstitution required; store in refrigerator (2–8°C); may be kept at room temperature (up to 30°C) for maximum 14 days prior to use

Dulaglutide; Type 2 diabetes; GLP-1 receptor agonist; incretin mimetic; once-weekly injection; cardiovascular benefit; weight loss; renal-safe; pregnancy-avoid; Schedule H India

RxIndia v1.0 — 25 Jan 2025

• CDSCO — Approved Formulations Database

• Trulicity India Product Insert (Eli Lilly)

• National Formulary of India (NFI)

• ICMR Guidelines for Management of Type 2 Diabetes

• RSSDI Clinical Practice Recommendations for Management of Type 2 Diabetes

• API Textbook of Medicine

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine

• REWIND Trial (for cardiovascular outcome data — off-label evidence reference)