What are the indications, dosage, and adverse effects of Tirzepatide (Glucagon-like peptide-1 (GLP-1) receptor agonist)?

From the Guidelines

Tirzepatide is a dual GIP/GLP-1 receptor agonist that should be initiated at a dose of 2.5 mg subcutaneously once weekly for 4 weeks, then increased to 5 mg weekly, with possible escalation to 10 mg or 15 mg based on glycemic response, and is approved for type 2 diabetes management and weight loss. For weight management, the same initial dosing applies, with gradual increases to a target dose of 15 mg weekly. The indications for tirzepatide include type 2 diabetes management and weight loss in adults with obesity. Common adverse effects of tirzepatide include gastrointestinal symptoms like nausea, vomiting, diarrhea, and constipation, which typically improve over time, as reported in a study published in the Journal Anaesthesia 1. More serious potential side effects include pancreatitis, gallbladder disease, hypoglycemia (especially when used with insulin or sulfonylureas), and kidney injury, as noted in a review published in the Annals of Internal Medicine 1. Tirzepatide is contraindicated in patients with personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2, and should be used cautiously in patients with diabetic retinopathy. The medication works by activating both GIP and GLP-1 receptors, enhancing insulin secretion, reducing glucagon levels, slowing gastric emptying, and decreasing appetite, resulting in improved glycemic control and weight reduction, as described in a study published in JAMA 1. A recent meta-analysis of RCTs that included 12,371 adults with overweight or obesity without diabetes reported that 15 mg weekly of tirzepatide was associated with greater weight loss compared with 2.4 mg weekly of subcutaneous semaglutide and 3 mg daily of subcutaneous liraglutide, as reported in a study published in JAMA 1. The dosage of tirzepatide should be adjusted based on kidney function, and the medication should be used with caution in patients with kidney impairment, as noted in a review published in the Annals of Internal Medicine 1. In terms of quality of life, tirzepatide has been shown to improve weight loss and glycemic control, which can lead to improved overall health and well-being, as reported in a study published in the Journal Anaesthesia 1. However, the medication can also cause gastrointestinal side effects, which can negatively impact quality of life, as noted in a review published in the Annals of Internal Medicine 1. Overall, tirzepatide is a valuable treatment option for adults with type 2 diabetes and obesity, but should be used under the guidance of a healthcare provider and with careful monitoring of potential side effects. Some key points to consider when prescribing tirzepatide include:

• Starting dose: 2.5 mg subcutaneously once weekly for 4 weeks
• Target dose: 15 mg weekly
• Contraindications: personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2
• Caution: diabetic retinopathy, kidney impairment
• Common adverse effects: gastrointestinal symptoms, pancreatitis, gallbladder disease, hypoglycemia, kidney injury
• Quality of life: improved weight loss and glycemic control, but potential gastrointestinal side effects.

From the FDA Drug Label

The effectiveness of MOUNJARO as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus was established in five trials In these trials, MOUNJARO was studied as monotherapy (SURPASS-1); as an add-on to metformin, sulfonylureas, and/or sodium-glucose co-transporter 2 inhibitors (SGLT2 inhibitors) (SURPASS-2, -3, and -4); and in combination with basal insulin with or without metformin (SURPASS-5) In adult patients with type 2 diabetes mellitus, treatment with MOUNJARO produced a statistically significant reduction from baseline in HbA1c compared to placebo MOUNJARO has a pH of 6.5 – 7.5. Each single-dose pen or single-dose vial contains a 0.5 mL solution of 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, or 15 mg of tirzepatide Tirzepatide lowers fasting and postprandial glucose concentration, decreases food intake, and reduces body weight in patients with type 2 diabetes mellitus. The most common adverse reactions reported in ≥5% of patients treated with MOUNJARO are not specified in the provided text, but it is mentioned that more MOUNJARO-treated patients who developed anti-tirzepatide antibodies experienced hypersensitivity reactions or injection site reactions than those who did not develop these antibodies.

• Indications:
  • Improvement of glycemic control in adults with type 2 diabetes mellitus
• Dosage:
  • 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, or 15 mg of tirzepatide once weekly
• Adverse effects:
  • Hypersensitivity reactions
  • Injection site reactions
  • Other adverse reactions are not specified in the provided text, but it is mentioned that patients with renal impairment may experience severe adverse gastrointestinal reactions. 2

From the Research

Indications and Dosage of Tirzepatide

• Tirzepatide is approved for use as an adjunct to diet and exercise to improve glycaemic control in adults with type 2 diabetes mellitus (T2DM) 3, 4, 5, 6, 7
• The recommended dosage of tirzepatide is 5-15 mg per week, administered via subcutaneous injection 4, 5, 6
• Tirzepatide can be used as monotherapy or in combination with other glucose-lowering medications, including oral medications and insulin 3, 4, 5, 6, 7

Adverse Effects of Tirzepatide

• The most common adverse events associated with tirzepatide are gastrointestinal events, including nausea, diarrhoea, decreased appetite, and vomiting 3, 4, 5, 6
• Tirzepatide is associated with a low risk of clinically significant or severe hypoglycaemia 3, 4, 5, 6
• The incidence of hypoglycaemia with tirzepatide is similar to that of placebo and lower than that of basal insulin 6
• Tirzepatide may also be associated with an increased risk of gastrointestinal adverse events, including nausea, vomiting, and diarrhoea, particularly at higher doses 6

Efficacy of Tirzepatide

• Tirzepatide has been shown to be effective in reducing HbA1c and body weight in adults with T2DM 3, 4, 5, 6, 7
• Tirzepatide has been demonstrated to be superior to other glucose-lowering medications, including GLP-1 receptor agonists and basal insulin, in terms of glycaemic control and weight loss 3, 4, 5, 6, 7
• The efficacy of tirzepatide is dose-dependent, with higher doses associated with greater reductions in HbA1c and body weight 4, 5, 6