Introduction: A New Era in Metabolic Therapy
Obesity and type 2 diabetes (T2D) have reached epidemic proportions worldwide, driving an urgent need for more effective treatments. Traditional approaches yielded only modest weight loss, but recent breakthroughs in incretin-based therapies are transforming outcomes. The latest game-changer is tirzepatide, a first-in-class dual incretin agonist targeting both GIP and GLP-1 receptors. In clinical trials, tirzepatide helped patients lose 15–22% of body weight on average – approaching results once seen only with bariatric surgery. Such unprecedented efficacy has energized the pharmaceutical industry and ignited a global race to develop next-generation metabolic drugs. At the same time, the commercial opportunity is immense: for example, Novo Nordisk’s GLP-1 analog semaglutide (Ozempic®/Wegovy®) generated ~$29.3 billion in 2024, accounting for 70% of the company’s revenue. Now tirzepatide (Eli Lilly’s Mounjaro®/Zepbound™) is rapidly gaining ground with $16.5 billion in first-year sales (2024) across its diabetes and obesity indications. This article explores how tirzepatide works and why its dual GIP/GLP-1 mechanism is revolutionary, reviews key clinical data, and considers the market and partnership implications of this dual-incretin breakthrough.
Figure 1. Mechanism of action of tirzepatide: dual activation of GIP and GLP-1 receptors enhances insulin secretion, suppresses glucagon release, delays gastric emptying, and reduces appetite. This synergistic incretin signaling contributes to superior glycemic control and weight loss.
(Adapted from Fisman & Tenenbaum, 2021, Cardiovascular Diabetology)
From GLP-1 to Dual-Target: The Science Behind Incretins
Glucagon-like peptide-1 (GLP-1) receptor agonists have already proven the power of harnessing gut hormones. GLP-1 analogues (e.g. semaglutide, liraglutide) promote insulin release, slow gastric emptying, reduce glucagon, and act on the brain to suppress appetite, leading to improved glycemic control and significant weight loss. However, GLP-1 is only one piece of the puzzle. Tirzepatide introduces a “twincretin” approach by also targeting glucose-dependent insulinotropic polypeptide (GIP) receptors. GIP is another incretin hormone that stimulates insulin secretion and affects fat metabolism, though in T2D patients its activity is blunted. By activating both incretin pathways, tirzepatide achieves complementary and enhanced effects.
Notably, preclinical and clinical studies confirm that dual GIP/GLP-1 agonism yields superior glucose lowering and weight reduction compared to GLP-1–only therapy. Scientists hypothesize this is because GIP and GLP-1 receptors have overlapping yet distinct expression in metabolic organs and the brain. Tirzepatide’s dual receptor activation engages broader neural circuits that regulate appetite and satiety. As the authors of a recent NEJM study explain, “both treatments decrease appetite… The patterns of central expression of GIP receptors do not fully overlap with those of GLP-1 receptors, and this variation is hypothesized to contribute to the higher weight reduction noted with dual agonism… than with agonism of either receptor alone”. In simpler terms, tirzepatide hits two metabolic “switches” instead of one – leading to synergistic benefits in controlling blood sugar and body weight. This mechanistic innovation set the stage for its remarkable clinical success.
Tirzepatide’s Clinical Breakthrough: Diabetes and Obesity
Figure 2. Change in body weight (%) over 72 weeks in the SURMOUNT-3 trial. Tirzepatide demonstrated continued weight loss following a lifestyle lead-in phase, with participants achieving an average of 18–21% reduction in body weight. These results reflect tirzepatide’s powerful effect in sustaining and enhancing prior diet-induced weight loss.
(Source: Nature Medicine, 2023)
Tirzepatide garnered global attention through the SURPASS and SURMOUNT clinical trial programs, which demonstrated unprecedented outcomes in both T2D and obesity:
Type 2 Diabetes (SURPASS trials): In a Phase 3 trial of T2D patients (SURPASS-1), once-weekly tirzepatide monotherapy caused “robust improvements in glycemic control and bodyweight”. At 40 weeks, high-dose tirzepatide lowered HbA1c by ~2.0 percentage points (from ~7.9% to ~5.8%) versus virtually no change on placebo. Strikingly, 31–52% of tirzepatide-treated patients achieved normal A1c levels (HbA1c <5.7%), compared to just 1% on placebo. This was accompanied by a dose-dependent weight loss of ~7–9.5 kg (≈11% of body weight) with tirzepatide, far exceeding the negligible weight change in the control group. Many patients on tirzepatide achieved clinically meaningful weight reduction (e.g. ≥10% body weight loss) even as their blood sugar normalized. Importantly, these benefits came without increased hypoglycemia risk, since incretin-based actions remain glucose-dependent. The safety profile – mostly mild-to-moderate gastrointestinal side effects such as nausea and diarrhea – was similar to established GLP-1 therapies. In head-to-head trials, tirzepatide also outperformed the GLP-1 agonist dulaglutide in T2D, confirming its superior efficacy on both A1c and weight endpoints.
Obesity/Weight Management (SURMOUNT trials): Tirzepatide’s results in obese participants (without diabetes) have been nothing short of groundbreaking. The Phase 3 SURMOUNT-1 trial reported average weight reductions of 15.0%, 21.4%, and 22.5% with tirzepatide (5 mg, 10 mg, 15 mg doses respectively) over 72 weeks, compared to just 2.4% with placebo. Highest-dose tirzepatide patients lost 22.5% of their body weight on average (about 24 kg or 52 lbs). Moreover, 9 out of 10 patients on tirzepatide achieved at least a 5% weight loss (a clinically significant threshold), vs only 28% on placebo. Over half of those on tirzepatide 10 or 15 mg lost ≥20% of body weight, an outcome virtually unheard of with medications until now. Equally impressive, one-third to nearly 40% of high-dose patients reached ≥25% weight loss – approaching the typical efficacy of metabolic surgery. These results, published in New England Journal of Medicine in 2022, cemented tirzepatide’s status as a potential “best-in-class” obesity therapy. Subsequent SURMOUNT trials extended these findings: for instance, SURMOUNT-2 (in patients with obesity and T2D) still achieved up to ~16% weight reduction at the highest dose – a remarkable outcome given that weight loss is often harder to attain in diabetic patients. In SURMOUNT-3 and -4, which included intensive lifestyle lead-in phases, tirzepatide helped participants not only sustain prior diet-induced losses but lose an additional ~18–21% body weight over ~72 weeks. Even when tirzepatide was withdrawn, those who had been on the medication regained far less weight than the placebo group, underscoring tirzepatide’s role in long-term weight regulation.
Head-to-Head vs. Semaglutide: Given semaglutide’s success, a critical question was how tirzepatide compares directly to the leading single-incretin therapy. The recent SURMOUNT-5 trial (2025) provided answers. In this 72-week study of obese adults, tirzepatide produced a 20.2% mean weight reduction vs 13.7% with semaglutide (both at max tolerated doses). In other words, tirzepatide led to ~47% greater average weight loss than semaglutide, a statistically and clinically significant improvement. Additionally, a far higher proportion of tirzepatide patients hit deeper weight-loss milestones (≥10%, ≥15%, ≥20%, ≥25% loss) compared to those on semaglutide. Both treatments improved blood pressure, lipids, and other metabolic risk factors as weight fell, but the extra weight loss with tirzepatide conferred incremental benefits on these health metrics. Notably, tolerability was comparable or better with the dual agonist: GI side effects were mostly mild and occurred during dose-escalation, and drop-out rates due to adverse events were actually lower for tirzepatide than for semaglutide in this trial. These head-to-head data firmly establish tirzepatide as more effective than the current standard for medical weight management, validating the value of dual-incretin targeting in obesity care.
With such outcomes, regulators moved swiftly: tirzepatide was first approved in 2022 for T2D, and by late 2023 it became the first-ever dual GIP/GLP-1 agonist approved for chronic weight management in adults (U.S. FDA). In its obesity indication, branded as Zepbound™, tirzepatide is indicated for patients with BMI ≥30 (or ≥27 with comorbidities) who need to lose weight. The dual-incretin revolution had officially begun.
Market Impact: Opportunity & Competition
Figure 3. Global market size projection for GLP-1 receptor agonists in weight loss, 2022–2030. The market is expected to grow at a CAGR of over 16%, driven by increasing demand for obesity therapeutics like semaglutide and tirzepatide. Dual- and triple-agonist therapies are poised to lead this growth.
(Source: Grand View Research, 2024)
The commercial impact of GLP-1 and dual-incretin therapies is already enormous and still accelerating. As noted, semaglutide and tirzepatide are generating tens of billions in revenue annually, reflecting the high demand for effective obesity and diabetes medications. The global anti-obesity drug market is projected to explode from about $12.8 billion in 2024 to $104.9 billion by 2035, a staggering ~21% CAGR. This growth is fueled largely by incretin-based drugs – with semaglutide and tirzepatide leading the charge – as well as emerging agents (small-molecule or biologics) targeting similar pathways. Analysts estimate that incretin therapies could become some of the highest-selling drugs in pharma history, and multiple companies are scrambling to capture share. In fact, a recent analysis projected that five GLP-1/T2D products could collectively amass hundreds of billions in sales by 2030 if current trends continue.
This lucrative market has spurred a wave of R&D and partnerships. Several pharmaceutical players beyond Novo Nordisk and Lilly are investing in next-generation metabolic therapies. For example, triple agonists that activate GIP, GLP-1 and glucagon receptors (such as Lilly’s retatrutide) are in development, aiming to push efficacy even further. Early Phase 2 data for retatrutide showed dose-dependent weight loss up to 24% at 48 weeks – even higher than tirzepatide’s phase 2 results – along with impressive glucose lowering. Likewise, combination regimens (e.g. GLP-1 agonist + amylin analog) and oral incretin drugs (like oral GLP-1 agonists) are being explored to broaden patient options. The competitive landscape will intensify as new entrants seek to dethrone the current market leaders or carve out niches (for instance, Pfizer and Amgen are developing oral GLP-1 receptor agonists, and Amgen is testing a differentiated dual agonist AMG133 that antagonizes GIP while agonizing GLP-1).
Amid this booming sector, it’s not just about innovation in the clinic – manufacturing and supply chain capacity have become critical. Incretin therapies like semaglutide and tirzepatide are complex peptide drugs, historically expensive to produce. Meeting global demand requires scalable peptide synthesis or biomanufacturing, robust quality control, and regulatory compliance across many markets. This is leading companies to form partnerships for production, formulation technology, and distribution to accelerate scale-up and market reach. There are also strategic collaborations as big pharma scouts for promising pipeline assets (e.g. licensing deals with biotech innovators working on novel obesity treatments). For instance, Lilly acquired rights to retatrutide (internally developed) and other candidates, while competitors like Novo Nordisk are actively in-licensing or acquiring next-gen candidates to sustain their dominance.
Leveraging Unibest’s Strengths in the Incretin Era
For overseas pharmaceutical companies – especially those looking to ride the GLP-1/GIP therapy wave – partnering with experienced, resource-rich organizations is key to success. Unibest Industrial Co., Ltd. (Unibest) offers a unique gateway to China’s vast pharmaceutical resources and a proven track record of global collaboration. With over 20 years in the pharma industry, Unibest has built an extensive network of high-quality Chinese suppliers and manufacturers, along with rich experience in exporting finished dosage forms and active ingredients worldwide. This positions us as an ideal ally for companies aiming to develop, manufacture, or source products in the GLP-1 and dual-incretin space.
Our one-stop service portfolio covers the entire value chain, from R&D support and sourcing of raw materials to regulatory affairs and licensing deals. Some key advantages include:
Broad Product Coverage: Unibest can assist with finished drug products (both chemical and biologic), active pharmaceutical ingredients (APIs), intermediates, and even pharmaceutical excipients. For example, we supply critical intermediates and starting materials for innovative peptides like semaglutide and tirzepatide. (See our Human Pharma Intermediates catalog and API catalog for the extensive range of products available). Through close partnerships with GMP-certified manufacturers, we ensure these ingredients meet the stringent quality standards required for production of incretin drugs. Our emphasis on rigorous quality control at every step – from synthesis and purification to packaging – gives partners confidence in the consistency and safety of the supply. At the same time, our deep local network enables cost-effective sourcing, passing on significant cost savings to our clients without compromising quality (as outlined in our Cost Saving approach).
Innovation & Pipeline Licensing: Beyond commercial supply, Unibest actively engages in pharmaceutical innovation and global licensing opportunities. We maintain a curated list of new drug candidates open for licensing or co-development – the Unibest NewCo & Licensing Pipeline features assets ranging from oncology to metabolic diseases. Notably, Unibest is investing in the incretin field itself. For instance, we have launched an innovative semaglutide program (codenamed UB-PEP-104), exploring a novel 505(b)(2) development for semaglutide (e.g. alternative formulations or delivery methods). We also offer a proprietary Semagcare product line – high-quality semaglutide tablets (3mg, 7mg, 14mg) – through a partnership that leverages advanced peptide manufacturing and an IP strategy to bring affordable oral semaglutide to emerging markets. These initiatives reflect our commitment to making breakthrough treatments more accessible globally. If you are seeking to license-in cutting-edge obesity/diabetes candidates or looking for a partner to license-out your own assets in these areas, Unibest’s NewCo/Licensing team can facilitate win-win collaborations. (See our NewCo & License Out service page for how we bridge Chinese innovation with global markets.)
Regulatory and Development Support: Successfully launching a new therapy in international markets requires navigating complex regulatory landscapes. Unibest’s experienced regulatory affairs team offers end-to-end support, including Drug Substance (DS) and Drug Product (DP) registration services for various countries. We have expertise in compiling high-quality dossiers, managing submissions, and ensuring compliance with local regulations – streamlining the approval process for our partners (learn more about our DS & DP Registration service). Furthermore, our development capabilities (from formulation to tech transfer) mean we can help scale up manufacturing or establish technology transfer (Tech Transfer) for production in your target market. For example, Unibest can facilitate the transfer of know-how for producing semaglutide or tirzepatide in a cost-effective way once patents expire or for authorized generic production in certain regions. We pride ourselves in offering comprehensive solutions that reduce risk and accelerate time-to-market – whether it’s through contract development & manufacturing (CDMO) support, or connecting you with the right local partners for distribution and commercialization.
In summary, Unibest is fully prepared to support global pharma companies in capitalizing on the GIP/GLP-1 dual-agonist revolution. We combine the latest scientific insights with practical industry know-how – from ensuring a stable supply of high-purity peptide components to identifying promising new co-agonist molecules for licensing. Our mission is to bridge Chinese pharmaceutical innovation and cost advantages with the needs of international partners, thereby jointly delivering life-changing therapies to patients worldwide.
Conclusion
The emergence of tirzepatide and other dual-incretin therapies represents a paradigm shift in treating obesity and type 2 diabetes. By simultaneously targeting multiple metabolic pathways, these drugs are achieving outcomes once thought unattainable with medication alone – profoundly improving patients’ weight, glycemic control, and overall health. The clinical success of tirzepatide has not only benefited individuals living with obesity/diabetes, but also validated a new therapeutic strategy that is inspiring an array of next-generation drugs. As the pipeline expands (with triple agonists and combination approaches on the horizon), the coming years promise even more innovation in this space.
For pharmaceutical companies worldwide, the dual incretin revolution offers tremendous opportunity – but seizing it will require the right expertise, partnerships, and resources. Whether the goal is to develop a novel compound, produce an established one at scale, or expand a product’s global footprint, collaboration is key. Unibest is proud to be a part of this exciting journey. With our two decades of experience and integrated services, we stand ready to help our partners navigate the scientific, technical, and commercial challenges of obesity and diabetes therapeutics. Together, we can leverage breakthrough mechanisms like GIP/GLP-1 co-agonism to deliver better treatments to the hundreds of millions in need, while also achieving shared success in this dynamic and fast-growing market.
Let’s embrace this new era of mechanism and clinical innovation – and, through strategic partnership, turn scientific advances into real-world therapies that improve lives across the globe.
References
1、Rosenstock, J. et al. (2021). Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1). The Lancet, 398(10295), 143–155. DOI: 10.1016/S0140-6736(21)01324-6
2、Jastreboff, A.M. et al. (2022). Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). New England Journal of Medicine, 387(3), 205–216. DOI: 10.1056/NEJMoa2206038 (Summary via Eli Lilly press release)
3、Aronne, L. et al. (2025). Tirzepatide vs. Semaglutide for Weight Management (SURMOUNT-5). New England Journal of Medicine. DOI: 10.1056/NEJMoa2416394 (reported in Applied Clinical Trials, May 12, 2025)
4、Eli Lilly and Company. Press Release: Zepbound™ (tirzepatide) showed superior weight loss over Wegovy® (semaglutide) – SURMOUNT-5 results. May 11, 2025
5、FDA News Release. FDA Approves Lilly’s Zepbound™ (tirzepatide) for Chronic Weight Management. Nov 8, 2023
6、Research and Markets. Global Anti-Obesity Drugs Market Forecast 2024–2035 – Key Trends. Globe Newswire. March 17, 2025
7、Huateng Pharma. Semaglutide & Tirzepatide: Leading GLP-1 Drug Sales in 2024. (Market report, Feb 2025)
8、Melson, E. et al. (2025). What is the pipeline for future medications for obesity? International Journal of Obesity, 49, 433–451. (Highlights on retatrutide and other multi-agonists)
9、World Health Organization (2022). World Obesity Day – News Release: “More than 1 billion people worldwide are obese – 650 million adults, 340 million adolescents and 39 million children…”
