Tirzepatide Reduces Appetite, Energy Intake, and Fat Mass in People With Type 2 Diabetes

Heise, Tim; DeVries, J. Hans; Ohwaki, Kenji; Li, Jing; Pratt, Edward John; Thomas, Melissa K.; Mather, Kieren J.; Karanikas, Chrisanthi A.; Dunn, Julia P.; Haupt, Axel; Miličević, Zvonko; Coşkun, Tamer

doi:10.2337/dc22-1710

Cited by 53 publications

(35 citation statements)

References 9 publications

(13 reference statements)

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“…Furthermore, 81%‐97% of participants achieved an HbA1c of less than 7.0% and 23%‐62% achieved an HbA1c of less than 5.7% 3–7 . In a mechanism‐of‐action study in people with T2D, tirzepatide was shown to improve glycaemic control by enhancing pancreatic beta‐cell function, improving insulin sensitivity and suppressing glucagon secretion, 8 as well as reducing food intake 9 …”

Section: Introductionmentioning

confidence: 99%

“…[3][4][5][6][7] In a mechanismof-action study in people with T2D, tirzepatide was shown to improve glycaemic control by enhancing pancreatic beta-cell function, improving insulin sensitivity and suppressing glucagon secretion, 8 as well as reducing food intake. 9 The robust glycaemic control observed with tirzepatide treatment in the phase 3 global registration trials (SURPASS-1 through SURPASS-5) was associated with clinically meaningful body weight reductions. [3][4][5][6][7] Study participants treated with tirzepatide lost on average 6-13 kg (7%-14%) of body weight.…”

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confidence: 99%

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Relationship between body weight change and glycaemic control with tirzepatide treatment in people with type 2 diabetes: A post hoc assessment of the SURPASS clinical trial programme

Pedersen

Giorgino

Umpiérrez

et al. 2023

Diabetes Obesity Metabolism

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Aim: To assess the relationship between HbA1c and body weight reductions with tirzepatide treatment (5, 10 or 15 mg).Materials and Methods: HbA1c and body weight data at 40 weeks (SURPASS-1, -2 and -5) and 52 weeks (SURPASS-3 and -4) were analysed by trial.Results: Across the SURPASS clinical trials, HbA1c reductions from baseline were observed in 96%-99%, 98%-99% and 94%-99% of participants treated with tirzepatide 5, 10 and 15 mg, respectively. Moreover, 87%-94%, 88%-95% and 88%-97% of participants, respectively, experienced weight loss associated with HbA1c reductions. Statistically significant associations (correlation coefficients ranging from 0.1438 to 0.3130 across studies; P ≤ .038) between HbA1c and body weight changes were observed with tirzepatide in SURPASS-2, -3, -4 (all doses) and -5 (tirzepatide 5 mg only). Conclusions:In this post hoc analysis, consistent reductions in both HbA1c and body weight were observed in most participants treated with tirzepatide at doses of 5, 10 or 15 mg. A statistically significant but modest association between HbA1c and body weight change was observed in SURPASS-2, SURPASS-3 and SURPASS-4, suggesting that both weight-independent and weight-dependent mechanisms are responsible for the tirzepatide-induced improvement in glycaemic control.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

Relationship between body weight change and glycaemic control with tirzepatide treatment in people with type 2 diabetes: A post hoc assessment of the SURPASS clinical trial programme

Pedersen

Giorgino

Umpiérrez

et al. 2023

Diabetes Obesity Metabolism

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“…Tirzepatide is a single molecule that combines glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonism resulting in synergistic effects on appetite, food intake, and metabolic function . Tirzepatide is approved in many countries, including the US, EU, and Japan, as a once-weekly subcutaneous injectable for type 2 diabetes and for the treatment of obesity in the US and UK . In a placebo-controlled trial of participants with obesity or overweight without diabetes, tirzepatide led to mean reductions in body weight up to 20.9% after 72 weeks of treatment …”

Section: Introductionmentioning

confidence: 99%

Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity

Aronne,

Sattar,

Horn

et al. 2024

JAMA

106

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ImportanceThe effect of continued treatment with tirzepatide on maintaining initial weight reduction is unknown.ObjectiveTo assess the effect of tirzepatide, with diet and physical activity, on the maintenance of weight reduction.Design, Setting, and ParticipantsThis phase 3, randomized withdrawal clinical trial conducted at 70 sites in 4 countries with a 36-week, open-label tirzepatide lead-in period followed by a 52-week, double-blind, placebo-controlled period included adults with a body mass index greater than or equal to 30 or greater than or equal to 27 and a weight-related complication, excluding diabetes.InterventionsParticipants (n = 783) enrolled in an open-label lead-in period received once-weekly subcutaneous maximum tolerated dose (10 or 15 mg) of tirzepatide for 36 weeks. At week 36, a total of 670 participants were randomized (1:1) to continue receiving tirzepatide (n = 335) or switch to placebo (n = 335) for 52 weeks.Main Outcomes and MeasuresThe primary end point was the mean percent change in weight from week 36 (randomization) to week 88. Key secondary end points included the proportion of participants at week 88 who maintained at least 80% of the weight loss during the lead-in period.ResultsParticipants (n = 670; mean age, 48 years; 473 [71%] women; mean weight, 107.3 kg) who completed the 36-week lead-in period experienced a mean weight reduction of 20.9%. The mean percent weight change from week 36 to week 88 was −5.5% with tirzepatide vs 14.0% with placebo (difference, −19.4% [95% CI, −21.2% to −17.7%]; P &lt; .001). Overall, 300 participants (89.5%) receiving tirzepatide at 88 weeks maintained at least 80% of the weight loss during the lead-in period compared with 16.6% receiving placebo (P &lt; .001). The overall mean weight reduction from week 0 to 88 was 25.3% for tirzepatide and 9.9% for placebo. The most common adverse events were mostly mild to moderate gastrointestinal events, which occurred more commonly with tirzepatide vs placebo.Conclusions and RelevanceIn participants with obesity or overweight, withdrawing tirzepatide led to substantial regain of lost weight, whereas continued treatment maintained and augmented initial weight reduction.Trial RegistrationClinicalTrials.gov Identifier: NCT04660643

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“…The effects of diet-induced weight loss on nonfat body compartments has come into focus with two recent developments. First, new highly effective weight-loss agents for treating people with obesity are accompanied by relatively large changes in fat-free mass (FFM) [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

“…The effects of diet‐induced weight loss on nonfat body compartments has come into focus with two recent developments. First, new highly effective weight‐loss agents for treating people with obesity are accompanied by relatively large changes in fat‐free mass (FFM) [5–8]. FFM includes the body's main functional tissues and organs, including SM, and excessive loss is viewed as an adverse pharmacologic effect [9–12].…”

Section: Introductionmentioning

confidence: 99%

Proportion of caloric restriction‐induced weight loss as skeletal muscle

Heymsfield,

Yang,

McCarthy

et al. 2023

Obesity

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ObjectiveThis study's objective was to develop models predicting the relative reduction in skeletal muscle (SM) mass during periods of voluntary calorie restriction (CR) and to validate model predictions in longitudinally monitored samples.MethodsThe model development group included healthy nonexercising adults (n = 897) who had whole‐body SM mass measured with magnetic resonance imaging. Model predictions of relative SM changes with CR were evaluated in two longitudinal studies, one 12 to 14 weeks in duration (n = 74) and the other 12 months in duration (n = 26).ResultsA series of SM prediction models were developed in a sample of 415 males and 482 females. Model‐predicted changes in SM mass relative to changes in body weight (i.e., ΔSM/Δbody weight) with a representative model were (mean ± SE) 0.26 ± 0.013 in males and 0.14 ± 0.007 in females (sex difference, p < 0.001). The actual mean proportions of weight loss as SM in the longitudinal studies were 0.23 ± 0.02/0.20 ± 0.06 in males and 0.10 ± 0.02/0.17 ± 0.03 in females, similar to model‐predicted values.ConclusionsNonelderly males and females with overweight and obesity experience respective reductions in SM mass with voluntary CR in the absence of a structured exercise program of about 2 to 2.5 kg and 1 to 1.5 kg per 10‐kg weight loss, respectively. These estimates are predicted to be influenced by interactions between age and body mass index in males, a hypothesis that needs future testing.

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Tirzepatide Reduces Appetite, Energy Intake, and Fat Mass in People With Type 2 Diabetes

Cited by 53 publications

References 9 publications

Relationship between body weight change and glycaemic control with tirzepatide treatment in people with type 2 diabetes: A post hoc assessment of the SURPASS clinical trial programme

Relationship between body weight change and glycaemic control with tirzepatide treatment in people with type 2 diabetes: A post hoc assessment of the SURPASS clinical trial programme

Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity

Proportion of caloric restriction‐induced weight loss as skeletal muscle

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