Effect of tirzepatide on weight and metabolism in a multiethnic cohort with and without diabetes

Abstract

Obesity is defined as excessive fat accumulation that adversely affects health. Body mass index (BMI) is commonly used to classify overweight (BMI ≥25) and obesity (BMI ≥30). Over one billion people worldwide are affected by obesity.¹ In the United Arab Emirates (UAE), 40.1% of adults are overweight and 27.8% are obese.² Among children, overweight and obesity prevalence is 22.3% and 18.9%, respectively. Excess weight is associated with cardiometabolic diseases, mechanical stress and psychosocial challenges. In the UAE, type 2 diabetes affects 19.3% of Emirati nationals and 12.4% of expatriates.³ Weight loss through lifestyle changes, medication or surgery improves metabolic markers, with reductions >15% potentially leading to diabetes remission and lower mortality.⁴ Recent advances in pharmacotherapy, particularly GLP-1 receptor agonists (GLP-1 RAs) and dual GLP-1/GIP receptor agonists have led to significant weight loss.⁵ Tirzepatide, a dual GLP-1/GIP agonist, has demonstrated glycaemic efficacy and substantial weight loss in clinical trials. This study aims to assess weight changes, glycaemic effectiveness and cardiometabolic improvements in a multiethnic cohort using tirzepatide with and without type 2 diabetes in Dubai, UAE.

Our study provides real-world data on tirzepatide's effectiveness in a diverse multiethnic UAE cohort, including people with and without type 2 diabetes (T2DM). At 6 months, the average HbA1c reduction was 1.02%, with most participants on 5 or 7.5 mg doses (mean dose: 7.3 mg in people with type 2 diabetes, 6.8 mg in those without). This reduction is lower than the 1.9%–2.58% reported in the SURPASS trials,^{6, 7} which used higher doses and longer follow-up periods. However, our findings align with other real-world studies⁸ and reinforce tirzepatide's effectiveness in glycaemic control. Weight loss in our cohort was substantial, with an overall average reduction of 10.7% at 6 months (7.9% in people with type 2 diabetes and 13.8% in those without), closely resembling results from the SURPASS trials. This suggests that tirzepatide remains effective in promoting weight loss, even at lower doses and over a shorter duration. The findings also support prior observational studies showing reductions of 10.1%–14.5% in 6 months, with some variations due to dosing differences.⁹ Furthermore, meta-analyses confirm tirzepatide's efficacy in diverse populations. Improvements in cardiometabolic parameters, including LDL, AST and ALT, were observed—findings that are consistent with results from recent clinical trials.⁷ However, the reduction in systolic blood pressure was not statistically significant. These changes reflect broader findings from real-world data and meta-analyses. A subgroup analysis showed promising results in people with polycystic ovary syndrome, who experienced a 16.8% weight reduction despite 25.5% having type 2 diabetes.¹⁰ Similarly, people with a history of bariatric surgery and weight regain lost 13.8% of their weight, supporting the use of GLP-1 receptor agonists in managing weight regain.¹¹ Among users of psychiatric medications, weight loss was slightly lower (8.58%), consistent with prior studies suggesting a dampening effect of antidepressants on weight loss outcomes.¹² Our study strengthens the evidence for tirzepatide's role in weight and glycaemic management across a diverse population. However, its retrospective design, small sample size and short follow-up period of 6 months limit long-term conclusions. Further research is needed to assess sustainability, safety and the impact of tirzepatide on metabolic health over extended periods.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

MAS has served on ad-hoc advisory boards and has received speaker honoraria from Eli Lilly.