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Tirzepatide for weight loss

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

Glucagon-like peptide-1 (GLP-1) receptor agonists are an effective treatment option for patients with type 2 diabetes

  • act by stimulating insulin secretion in hyperglycemic states, suppressing glucagon secretion in hyperglycemic or euglycemic states, delaying gastric emptying, decreasing appetite, and reducing body weight

Tirzepatide

  • is a dual glucose-dependent insulinotropic polypeptide-GLP-1 receptor agonist
  • structure is primarily based on the glucose-dependent insulinotropic polypeptide amino acid sequence and includes a C20 fatty diacid moiety
    • C20 fatty di-acid moiety that prolongs the duration of action, thus allowing once-weekly subcutaneous administration
  • is a 39 amino acid synthetic peptide with agonist activity at both the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, with a greater affinity to GIP receptor
  • GIP, unlike GLP-1, it is glucagonotropic in a glucose-dependent manner
  • the efficacy and safety of once-weekly tirzepatide was compared with semaglutide, a selective GLP-1 receptor agonist (1)
    • estimated mean change from baseline in the glycated hemoglobin level was -2.01 percentage points, -2.24 percentage points, and -2.30 percentage points with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and -1.86 percentage points with semaglutide

    • reductions in body weight were greater with tirzepatide than with semaglutide (least-squares mean estimated treatment difference, -1.9 kg, -3.6 kg, and -5.5 kg, respectively; P<0.001 for all comparisons)

    • most common adverse events were gastrointestinal and were primarily mild to moderate in severity in the tirzepatide and semaglutide groups (nausea, 17 to 22% and 18%; diarrhea, 13 to 16% and 12%; and vomiting, 6 to 10% and 8%, respectively). Of the patients who received tirzepatide, hypoglycemia (blood glucose level, <54 mg per deciliter) was reported in 0.6% (5-mg group), 0.2% (10-mg group), and 1.7% (15-mg group); hypoglycemia was reported in 0.4% of those who received semaglutide

    • concluded that patients with type 2 diabetes, tirzepatide was noninferior and superior to semaglutide with respect to the mean change in the glycated hemoglobin level from baseline to 40 weeks

  • tirzepatide for weight loss
    • in SURMOUNT-1
      • double-blind, randomized, controlled trial
      • assigned 2539 adults with a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or more, or 27 or more and at least one weight-related complication, excluding diabetes, in a 1:1:1:1 ratio to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks, including a 20-week dose-escalation period
        • baseline, the mean body weight was 104.8 kg, the mean BMI was 38.0, and 94.5% of participants had a BMI of 30 or higher
        • mean percentage change in weight at week 72 was -15.0% (95% confidence interval [CI], -15.9 to -14.2) with 5-mg weekly doses of tirzepatide, -19.5% (95% CI, -20.4 to -18.5) with 10-mg doses, and -20.9% (95% CI, -21.8 to -19.9) with 15-mg doses and -3.1% (95% CI, -4.3 to -1.9) with placebo (P<0.001 for all comparisons with placebo)
        • 50% (95% CI, 46 to 54) and 57% (95% CI, 53 to 61) of participants in the 10-mg and 15-mg groups had a reduction in body weight of 20% or more
        • most common adverse events with tirzepatide were gastrointestinal, and most were mild to moderate in severity, occurring primarily during dose escalation
        • study authors concluded:
          • "..In this 72-week trial in participants with obesity, 5 mg, 10 mg, or 15 mg of tirzepatide once weekly provided substantial and sustained reductions in body weight.."
    • in SURMOUNT-2
      • 72-week trial in adults living with obesity and type 2 diabetes
        • once-weekly tirzepatide 10 mg and 15 mg provided substantial reduction in bodyweight (4)
          • mean change in bodyweight at week 72 with tirzepatide 10 mg and 15 mg was -12.8% and -14.7% , respectively, and -3.2% with placebo

In the UK, tirzepatide is now approved for use in adults with a BMI of 30kg/m² or more (obesity), as well as those with a BMI between 27-30kg/m² (overweight) who also have weight-related health problems such as prediabetes, high blood pressure, high cholesterol, or heart problems (5)

  • is advised that obese or overweight female patients using oral contraceptives should consider using a barrier method of contraception or switching to a non-oral contraceptive method for 4 weeks after starting tirzepatide and for 4 weeks after each increase in dose as it may affect efficacy of the contraceptive pill
  • starting dose is 2.5mg once a week for four weeks, increasing to 5mg once a week
  • dose may then be increased in at least 4-week intervals up to the maximum dose of 15mg once weekly

A review noted (2):

  • Tirzepatide is a novel incretin-based therapy for T2DM
    • showed robust HbA1c (-1.94%), FSG (-54.7 mg/dl), and body weight (-8.5 kg) reductions, without an increased risk of hypoglycemia
    • at the highest dose (15 mg), tirzepatide reduced: HbA1c (-2.1%), FSG (-61.1 mg/dl), and body weight (-8.6 kg)

Reference:

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