Tirzepatide proves more effective than insulin in diabetes and weight management in clinical trails

A recent meta-analysis involving over 4,300 participants has revealed that the once-weekly administration of tirzepatide, a novel treatment for type 2 diabetes (T2D), significantly reduces blood sugar levels, body weight, and cardiovascular risks more effectively than daily insulin. This breakthrough could mark a paradigm shift in the management of T2D, offering a more potent and efficient therapeutic option.

Research Overview

Published in the International Journal of Obesity, the meta-analysis assessed the efficacy and safety of tirzepatide, a new anti-diabetic and anti-obesity drug, in comparison to traditional long-acting and ultra-long-acting insulin therapies. This comprehensive evaluation was based on data extracted from the SURPASS-3, SURPASS-4, and SURPASS-AP-Combo randomised clinical trials, encompassing a total of 4,339 individuals and ten biochemical assessments.

The study’s findings suggest that tirzepatide not only meets but surpasses the efficacy and safety profile of conventional insulin treatments. This positions the drug as a potentially revolutionary alternative to current non-surgical interventions for managing type 2 diabetes.

Background on Type 2 Diabetes

Type 2 diabetes is a prevalent chronic condition characterised by elevated blood glucose levels, primarily due to insulin resistance. According to the International Diabetes Federation (IDF), approximately 10.5% of adults aged 20 to 79 are affected by diabetes, with type 2 diabetes being the most common form. This condition is closely linked to a range of serious comorbidities, including cardiovascular diseases (CVDs), certain cancers, and obesity.

The global burden of type 2 diabetes is increasing at an alarming rate. From 1990 to 2019, the prevalence of T2D surged by 27.4%, with mortality rates climbing by 47%. These trends underscore the urgent need for effective therapeutic interventions that can mitigate the risk factors associated with this disease. Research indicates that elevated body mass indices (BMIs) are the most significant contributors to T2D risk, making weight management a crucial focus in T2D treatment strategies.

However, many non-surgical interventions provide only short-term relief for individuals living with T2D, and the risk of adverse side effects remains high with current pharmacological treatments. This highlights the necessity for developing and validating new treatments that offer high efficacy with minimal risk. Tirzepatide is one such promising drug, with its dual agonist properties—targeting both glucagon-like peptides (GLP1s) and gastric inhibitory polypeptides (GIPs)—showing potential for unprecedented efficacy and sustained weight loss in preliminary trials.

Despite its promising profile, the long-term safety of tirzepatide in vivo remains to be fully validated. Establishing its effectiveness compared to conventional insulin therapies could facilitate its broader adoption, potentially revolutionising T2D treatment on a global scale.

Study Methodology

The present study employed a rigorous meta-analytic approach to compare the safety and efficacy of tirzepatide against conventional once-weekly insulin therapies in managing type 2 diabetes. Data for the meta-analysis were sourced from four major scientific repositories: PubMed, Scopus, Web of Science, and Google Scholar. The included studies specifically evaluated tirzepatide’s performance against insulin across various outcomes, including body weight, fasting glucose, haemoglobin A1c (HbA1c), blood sugar (BS), blood pressure (BP), triglycerides, and cholesterol (both total and lipoprotein fractions).

The study incorporated a detailed data extraction process, covering study characteristics, population demographics, intervention specifics, and outcome measures (both safety and performance). All extracted data were standardised before being subjected to meta-analysis.

To statistically compare the performance of insulin and tirzepatide, the researchers calculated the mean change, standard deviation (SD) change, odds ratios (ORs), and relative risks (RRs) for each outcome. Between-study heterogeneity was assessed using I2 statistics, and the risk of bias was evaluated with the Cochrane risk of bias tool.

Key Findings

Out of 705 publications initially identified, only three studies—SURPASS-3, SURPASS-4, and SURPASS-AP-Combo—met the stringent inclusion and exclusion criteria. These studies involved 4,339 participants, with 1,580 in the insulin cohort and 2,759 in the tirzepatide cohort.

“All included studies were multi-centre, randomised, open-label, parallel-group phase 3 clinical trials conducted in several countries. Three doses of tirzepatide (5 mg, 10 mg, and 15 mg) were used in all studies. Patients with type 2 diabetes aged 18 years or older were included in all studies.”

The analysis revealed that while selection, reporting, and attrition biases were low across the included studies, detection and performance biases were high due to the open-label design of the SURPASS trials. Despite these limitations, the meta-analysis demonstrated that tirzepatide (at doses of 5 mg, 10 mg, and 15 mg) significantly outperformed both long-acting and ultra-long-acting insulin therapies. Specifically, tirzepatide was associated with an average weight reduction of 10.61 kg, a decrease in systolic blood pressure by 6.47 mmHg, and a reduction in diastolic blood pressure by 2.3 mmHg. Additionally, there was a slight increase in pulse rate by 1.93 beats per minute (bpm).

Furthermore, tirzepatide significantly improved lipid profiles, including a reduction in triglycerides by 14.49% and decreases in total cholesterol (4.78%), LDL cholesterol (5.98%), and very low-density lipoprotein (VLDL) cholesterol (14.18%). These efficacy improvements were dose-dependent, with higher doses (10 mg and 15 mg) yielding greater benefits. The side effects associated with tirzepatide were found to be comparable to or lower than those observed with equivalent insulin doses.

“All in all, 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 achieve the 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

This meta-analysis underscores the superior safety and efficacy profile of tirzepatide compared to conventional long-acting and ultra-long-acting insulin therapies. The results indicate that tirzepatide achieves near-normal HbA1c levels in a significantly shorter time frame than insulin (8.1 weeks versus 12.1 weeks). Additionally, tirzepatide outperformed traditional pharmacological interventions across all ten evaluated metrics. While higher doses of tirzepatide were associated with a slightly increased risk of hypoglycaemia and nausea, these side effects were still comparable to or lower than those associated with insulin treatments.

Collectively, these findings suggest that tirzepatide could serve as a superior alternative to insulin, offering a more effective and potentially safer option for managing type 2 diabetes. As this drug becomes more widely adopted, it could transform the global landscape of diabetes treatment, offering new hope to millions of individuals living with this chronic condition.