Supported by a meta-analysis of more than 4,300 patients, once-weekly tirzepatide reduces blood sugar, weight and cardiovascular risks more effectively than daily insulin, offering a breakthrough alternative for the management of type 2 diabetes.
Study: Tirzepatide competes with long-acting insulin in the management of type 2 diabetes: a meta-analysis of three phase 3 randomized controlled trials. Image source: Dragana Gordic / Shutterstock
In a recent review and meta-analysis published in International Journal of Obesity, Researchers evaluated the safety and efficacy of once-weekly Tirzepatide, a revolutionary new anti-obesity and diabetes drug, versus conventional long- and ultra-long-acting insulin supplements in the management of type 2 diabetes (T2D). Their comprehensive data set was obtained from the SURPASS-3, SURPASS-4, and SURPASS-AP-Combo randomized clinical trials involving 4,339 patients and ten biochemical tests.
Study findings revealed that Tirzepatide matched or exceeded conventional once-weekly insulin supplements in both safety and efficacy. This highlights that the new drug could effectively replace non-surgical treatment options in the management of T2D.
Background
Diabetes is a chronic medical condition characterized by abnormal blood glucose concentrations due to reduced insulin secretion or effectiveness. Diabetes is one of the most common non-communicable diseases in the world, with the International Diabetes Federation (IDF) estimating that 10.5% of adults (aged 20-79) have diabetes. Type 2 diabetes (T2D) is the most common type of diabetes caused by insulin resistance. It is associated with a number of potentially fatal comorbidities, including cardiovascular disease (CVD), certain cancers, and obesity.
Alarmingly, the prevalence and mortality of T2D are increasing rapidly, with estimates reporting increases of 27.4% and 47%, respectively, in just 30 years (1990–2019). This makes T2D a public health concern of extremely high importance, necessitating extensive research into therapeutic interventions against its risk factors. Studies have revealed that high body mass indices (BMI) are the most important factors contributing to T2D risk, with a predominant portion of research targeting weight management as an indirect intervention against T2D.
Unfortunately, most non-surgical interventions against T2D have been found to offer only temporary (short-term) relief to patients. In addition, most pharmacological treatments have a high risk of unwanted side effects, which makes it imperative to discover and validate new treatments with high efficacy and low risk. Tirzepatide is one such next-generation drug that promises potentially unprecedented efficacy and long-term weight loss. It is a dual agonist with characteristics of both glucagon-like peptides (GLP1s) and gastric inhibitory polypeptides (GIPs). Preliminary clinical trials have highlighted its improved and long-lasting efficacy compared to placebos and conventional GIP and GLP1 agonists.
Despite its potentially revolutionary benefits, the in vivo The safety of Tirzepatide remains to be validated. Furthermore, establishing the efficacy of the once-weekly drug versus conventional once-weekly long-acting and ultra-long-acting insulin supplements would allow for its increased global adoption, thus revising the global treatment landscape for T2D.
About the study
This review seeks to use a rigorous meta-analytic approach to investigate the safety and efficacy of Tirzepatide versus conventional once-weekly insulin supplementation for the treatment of T2D. Data for the study were obtained from publications evaluating the safety or efficacy of Tirzepatide compared with insulin supplements in four online scientific repositories – PubMed, Scopus, Web of Science and Google Scholar.
Studies were included if they were clinical or randomized controlled trials that investigated the performance of Tirzepatide versus insulin on any of the following outcomes – Body weight, fasting glucose, hemoglobin A1c (HbA1c), blood sugar (BS), blood pressure (BP, systolic or diastolic), triglycerides and cholesterol (total, high or low density lipoprotein [HDL or LDL]). Data extraction included study characteristics, population measures, interventions and outcomes (safety or efficacy). All extracted data were converted to standardized units prior to meta-analysis.
To statistically evaluate the performance of insulin versus Tirzepatide, mean change, standard deviation (SD) change, odds ratios (ORs) and relative risks (RRs) were calculated for all outcomes. Between-study heterogeneity was calculated using I2 statistics and risk of bias was calculated using the Cochrane risk of bias tool.
Study findings
Of the 705 publications initially identified through title screening, abstract and full-text screening excluded 702, identifying only three studies (SURPASS-3, SURPASS-4, and SURPASS-AP-Combo randomized clinical trials) that met all inclusion criteria and exclusion. These three studies included 4,339 patients (insulin cohort = 1,580, Tirzepatide cohort = 2,759).
“All included studies were multicenter, randomized, open-label, parallel-group, phase 3 clinical trials conducted in multiple countries. All studies used three doses of tirzepatide (5 mg, 10 mg and 15 mg). All studies included patients with type 2 diabetes aged 18 years or older.”
The Cochrane risk of bias tool analysis revealed that while selection, reporting and attrition bias were low among the included studies, detection and attribution bias were high due to the SURPASS studies being open-label, unblinded studies. The results of the meta-analysis revealed that Tirzepatide (all three doses – 5, 10 and 15 mg) significantly outperformed long- and ultra-long-acting insulin supplements in reducing weight in T2D patients by 10.61 kg, blood pressure by 6.47 mmHg (systolic). and 2.3 mmHg (diastolic) and an increase in heart rate of 1.93 beats per minute (bpm).
In addition, Tirzepatide was observed to significantly improve measures of lipid profile such as reduction of triglycerides (14.49%) and cholesterol (total-4.78%, LDL-5.98% and very low density lipoprotein [VLDL]—14.18%). Efficacy was dose-dependent, with higher doses (10 and 15 mg) showing greater improvements. Tirzepatide side effects were generally found to be equal to or lower than those of equivalent doses of insulin.
“Overall, these findings suggest that, unlike long-acting insulin, tirzepatide maintains BS levels in a narrow and near-normal range and prevents fluctuations in BS levels. For example, analysis of data from the SURPASS-3 trial by Viljoen et al. revealed that the median time to first achieving HbA1c of 7.0% was 8.1 weeks for each dose of tirzepatide compared with 12.1 weeks for insulin degludec, suggesting an accelerated treatment response to Tirzepatide.
conclusions
The present meta-analysis highlights the safety and efficacy benefits of Tirzepatide over conventional long- and ultra-long-acting insulin supplements. The results reveal that Tirzepatide shows significantly shorter lag periods to achieve near-normal HbA1c measurements compared to insulin supplements (8.1 vs. 12.1 weeks). The new drug outperformed conventional pharmacological interventions in all ten measures investigated. Notably, while higher doses of Tirzapatide were associated with a slightly increased risk of hypoglycemia and nausea, these side effects were still equal to or lower than those seen with equivalent doses of insulin.
Together, these findings suggest that Tirzepatide can effectively replace insulin therapy as an improved clinical intervention for patients with T2D.
