Drug Database
GL

glucagon (LY 900018 / glucagon, Eli Lilly / Baqsimi)

✓ Approved

Amphastar Pharmaceuticals, Inc. · GCGR · Polypeptide

What is glucagon?

glucagon is a polypeptide developed by Amphastar Pharmaceuticals, Inc.. It is approved for therapeutic indications via inhaled or intramuscular (im) injection or intranasal.

Drug Profile

Brand NamesLY 900018, glucagon, Eli Lilly, Baqsimi
CompanyAmphastar Pharmaceuticals, Inc.
Drug ClassPolypeptide
Molecular TargetGCGR
RouteInhaled, Intramuscular (IM) Injection, Intranasal
StatusApproved
Sources: ClinicalTrials.gov, Amphastar Pharmaceuticals, Inc.

Mechanism of Action

Molecular Targets

glucagon acts on 1 molecular target:

GCGRglucagon receptor (GL-R, GGR)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

glucagon is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Metabolism and nutrition disordersHypoglycaemia✓ Approved

Related Research Articles

PubMedAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026-10-15

Loss of Intestinal MSTN Promotes GLP-1 Secretion Through SGLT1 Palmitoylation.

Han Sheng-Zhong SZ, Chang Shuang-Yan SY, Luo Zhaobo Z, Sun Ke K et al.

Intestinal glucagon-like peptide-1 (GLP-1) is secreted by intestinal L cells in a glucose-dependent manner. The localization and surface abundance of glucose-sensing proteins on the cell membrane affect the response to glucose, but the regulatory mechanism remains poorly understood. Here, we show that S-palmitoylation is required for stable plasma membrane enrichment of SGLT1 and for SGLT1-mediated GLP-1 secretion. Notably, myostatin (MSTN) was identified as a key upstream regulator of this modification. Intestinal MSTN deficiency markedly enhanced SGLT1 palmitoylation, increased its plasma membrane abundance, and thereby promoted glucose-stimulated GLP-1 secretion. Importantly, simvastatin induced intestinal MSTN upregulation and impaired glucose homeostasis, whereas MSTN deficiency largely alleviated these effects. Mechanistically, MSTN regulated the expression of the palmitoyl acyltransferase ZDHHC20, which catalyzed SGLT1 S-palmitoylation at Cys301. Blocking SGLT1 palmitoylation attenuated SGLT1 membrane enrichment and markedly suppressed the induction of GLP-1 secretion caused by MSTN deficiency. Collectively, our research results have revealed a new mechanism by which MSTN regulates intestinal endocrine function and S-palmitoylation modification promotes GLP-1 secretion, providing potential targets for regulating endogenous GLP-1 secretion in the intestine and treating metabolic diseases related to glucose imbalance.

PMID 42876031
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PubMedDiabetologia2026-10-15

Efficacy and safety of HRS-7535, a novel oral small-molecule glucagon-like peptide-1 receptor agonist, in participants with type 2 diabetes mellitus inadequately controlled by metformin and sodium-glucose co-transporter 2 inhibitors: a multicentre, randomised, double-blind, placebo-controlled, parallel-group Phase II trial.

Xu Mingtong M, Song Weihong W, Lv Fang F, Fu Yanqin Y et al.

This study aimed to evaluate the efficacy and safety of HRS-7535, an oral small-molecule glucagon-like peptide-1 receptor agonist (GLP-1RA), in Chinese participants with type 2 diabetes mellitus inadequately managed by metformin and sodium-glucose co-transporter 2 inhibitors (SGLT2i). This multicentre, randomised, double-blind, placebo-controlled, Phase II study included participants aged 18-75 years with type 2 diabetes, HbA1c 58-97 mmol/mol (7.5-11.0%) and BMI 20.0-35.0 kg/m2 and on stable-dose metformin and sodium-glucose co-transporter 2 (SGLT2) inhibitor therapy for ≥8 weeks prior to screening. Participants were assigned in a 1:1:1 ratio to receive HRS-7535 30 mg, HRS-7535 60 mg or visually matching placebo tablets once daily using a stratified block randomisation method, with treatment assignments concealed until study completion. The primary endpoint was the change in HbA1c from baseline to week 16. Secondary efficacy outcomes included the proportions of participants achieving HbA1c targets of <53 mmol/mol (7.0%) and ≤48 mmol/mol (6.5%), and changes from baseline in fasting body weight to week 16. A total of 155 participants with a mean baseline HbA1c of 69 mmol/mol (8.5%) were randomly assigned to HRS-7535 30 mg (n=51), HRS-7535 60 mg (n=53) or placebo (n=51). At week 16, the least‑squares mean differences in HbA1c from baseline for the HRS-7535 30 mg, HRS-7535 60 mg and placebo groups were -16 mmol/mol (95% CI -19, -14) (-1.5% [95% CI -1.7, -1.3]), -20 mmol/mol (95% CI -22, -17) (-1.8% [95% CI -2.0, -1.6]) and -4 mmol/mol (95% CI -7, -2) (-0.4% [95% CI -0.6, -0.2]), respectively (p<0.0001 for both HRS-7535 doses vs placebo). The proportions of participants achieving HbA1c <53 mmol/mol (7.0%) were 51.0% in the HRS‑7535 30 mg group, 66.0% in the HRS‑7535 60 mg group, and 9.8% in the placebo group; the corresponding proportions for HbA1c ≤48 mmol/mol (6.5%) were 35.3%, 37.7% and 3.9%, respectively. Body weight loss was -2.4% in the HRS-7535 60 mg group vs -0.7% in the placebo group. Most treatment-emergent adverse events (TEAEs) were mild to moderate, and gastrointestinal adverse events were the most common. No severe hypoglycaemia was reported. The only TEAE that led to treatment discontinuation occurred in the placebo group. Treatment with HRS-7535 resulted in significant improvements in glycaemic management in participants with type 2 diabetes, and the drug exhibited a favourable safety profile. To address a significant clinical data void, this research focused on the addition of HRS‑7535 to the background regimen of metformin and SGLT2i for glycaemic management in participants with type 2 diabetes. Trial registration ClinicalTrials.gov NCT06393348. Funding This study was funded by Jiangsu Hengrui Pharmaceuticals.

PMID 42875600
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PubMedDiabetes, obesity & metabolism2026-10-15

GLP-1 Receptor Agonist Therapy Is Associated With Lower Risk of Lower Extremity Amputation in Adults With Type 2 Diabetes and Foot Ulcer Without Coded Peripheral Arterial Disease: A Hypothesis-Generating Real-World Cohort Study.

Robinson Hani H, Yassin Mustafa M, Robinson Dror D, Eisa Mohamad M et al.

To compare lower extremity amputation (LEA) risk in adults with Type 2 diabetes and diabetic foot ulcer (DFU) treated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) versus other glucose-lowering therapy, and to test whether coded peripheral arterial disease (PAD) modifies this association and replicates across comparator classes. This new-user, active-comparator retrospective cohort study used the TriNetX Global Collaborative Network (queried 11 July 2026). Adults with Type 2 diabetes and DFU were propensity-score matched 1:1 on 22 covariates, giving 21 325 pairs for the primary comparison. Effect modification by coded PAD (ICD-10 I70.2) was examined in independently matched subgroups. Six sensitivity analyses were pre-specified: 30- and 180-day landmarks, all-cause mortality, background-therapy balancing, limb-severity adjustment and a broadened PAD definition. GLP-1 RA use was associated with lower 5-year LEA risk than all non-GLP-1 RA therapy (hazard ratio [HR]: 0.60, 95% CI: 0.54-0.67). The association was confined to the no-PAD stratum (HR: 0.21, 0.13-0.33) and absent where PAD was coded (HR: 0.97, 0.78-1.20); ratio of hazard ratios 0.21 (0.13-0.36; p < 0.001). All-cause mortality was also lower (HR: 0.48, 0.45-0.50). The insulin no-PAD estimate persisted under background-therapy balancing (0.14), limb-severity adjustment (0.16) and 30- and 180-day landmarks (0.28, 0.33). Broadening the PAD definition attenuated the no-PAD association without abolishing it (HR: 0.34, 0.17-0.65). In Type 2 diabetes with DFU, GLP-1 RA use was associated with lower LEA risk, surviving six pre-specified sensitivity analyses. These observational findings are hypothesis-generating and require prospective confirmation.

PMID 42875725
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PubMedDrugs2026-10-15

Metformin Lowers Fasting Hyperglycemia by Increasing Glucose Clearance in People with Moderately Controlled Type 2 Diabetes.

Kahl Sabine S, LaMoia Traci E TE, Jonuscheit Marc M, Heilmann Geronimo G et al.

Metformin is the most frequently prescribed antidiabetic drug worldwide; however, the mechanism by which it lowers blood glucose remains incompletely understood. The objective of this study was to examine the effects of metformin on whole-body and specifically on hepatic glucose and energy metabolism in type 2 diabetes. This open repeated-measures pilot study examined this question using Positional Isotopomer NMR Tracer Analysis (PINTA) to assess rates of endogenous glucose production (VEGP), hepatic pyruvate carboxylase flux (VPC), and citrate synthase (VCS) flux in 16 men with moderately controlled type 2 diabetes (T2D; BMI 30 ± 3 kg/m2, HbA1c 8.4 ± 1.4%) undergoing two examination days with (M+; 1 g twice daily) and without metformin (M-) treatment. Hepatic ATP and glycogen concentrations were quantified by 31P/13C magnetic resonance spectroscopy. M+ reduced fasting glycemia by 18%, which could mostly be attributed to a 24% increase in rates of whole-body glucose clearance. Surprisingly, these changes were accompanied by a 58% increase in VPC and a 34% increase in VCS, due to a 26% increase in plasma glucagon concentrations. The increase in VPC was offset by reductions in the contributions of glycerol conversion to glucose resulting in no change in VEGP. Metformin decreased hepatic ATP content by 16% and increased plasma GDF-15 concentrations, but did not alter rates of net hepatic glycogenolysis. Metformin treatment in male individuals of European ancestry with moderately controlled T2D decreases blood glucose concentrations by increasing rates of whole-body glucose clearance. Metformin further inhibits glycerol-derived gluconeogenesis, which is consistent with complex IV, not complex I, being the molecular target of metformin action. ClinicalTrials.gov ( https://clinicaltrials.gov/ ): NCT04088851.

PMID 42875657
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PubMedDiabetes, obesity & metabolism2026-10-15

Real-World Treatment Patterns and Weight Outcomes Before and After a Tirzepatide Price Increase in Over One Million Self-Paying UK Adults With Overweight or Obesity.

Dix Sophie S, Mulligan Anna A, Ficarelli Mattia M, Brooke Edward E et al.

Glucagon-like peptide-1 (GLP-1) receptor agonist-based medicines are highly effective treatments for overweight and obesity, but population-scale real-world evidence remains limited, particularly in self-funded settings where treatment choice may be influenced by relative price. We aimed to characterise provider reach and treatment patterns through a large United Kingdom (UK) telehealth provider, assess changes around the September 2025 tirzepatide list-price increase of up to 170%, and estimate longitudinal weight trajectories. A retrospective cohort study of adults initiating semaglutide or tirzepatide through MedExpress from 1 May 2024 to 1 January 2026 was conducted. Treatment initiation and switching were analysed using segmented interrupted time-series models, with sensitivity analyses addressing anticipatory changes in August 2025. Weight trajectories were estimated using linear mixed-effects models. Among 1 033 522 adults, 932 659 (90.2%) initiated tirzepatide and 100 863 (9.8%) semaglutide; provider reach was higher among women than men. In September 2025, semaglutide initiation increased by 31.15 percentage points (95% CI: 26.07-36.24) relative to the projected pre-interruption trend. Tirzepatide-to-semaglutide switching increased by 9.26 percentage points (95% CI: 7.09-11.42) and subsequently attenuated. Sensitivity analyses supported anticipatory changes in August. At 12 months, estimated weight loss was 19.93% with tirzepatide (95% CI: 19.88-19.98; n = 30 763) and 16.40% with semaglutide (95% CI: 16.16-16.64; n = 979). A single UK telehealth provider achieved substantial reach among adults with overweight or obesity. Treatment initiation and switching changed markedly around the tirzepatide price increase. Substantial longitudinal weight loss was observed among patients contributing follow-up in the context of limited adjunctive lifestyle support.

PMID 42875827
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PubMedFrontiers in cardiovascular medicine2026-10-15

GLP-1-Based therapies for obesity-related heart failure with preserved ejection fraction: an umbrella review incorporating broader heart failure and cardiometabolic evidence.

Li Qiang Q, Yang Tianyi T, Jin Guannan G, Zhou Yabin Y

The cardiometabolic phenotype of obesity-related heart failure with preserved ejection fraction (HFpEF) is increasing in clinical prevalence. Existing systematic reviews and meta-analyses have primarily summarized efficacy estimates for glucagon-like peptide-1 (GLP-1)-based therapies, but the credibility and independence of these syntheses remain uncertain because methodological limitations and overlap in primary trials have not been systematically evaluated. This umbrella review therefore appraised the methodological quality, overlap, consistency, and robustness of the existing review-level evidence rather than generating another efficacy synthesis. We conducted an umbrella review of systematic reviews, meta-analyses, and network meta-analyses evaluating GLP-1-based regimens in obesity-related HFpEF and adjacent cardiometabolic populations. PubMed, Embase, Web of Science, and the Cochrane Library were searched over the preceding decade. The systematic review or meta-analysis was the unit of analysis. Methodological quality was assessed with AMSTAR 2, and overlap of primary studies across reviews was quantified using the corrected covered area (CCA). No de novo meta-analysis was performed; primary trials were examined only to assess overlap and calculate the CCA. Review-level findings were synthesized according to effect direction, consistency, precision, sample size, methodological quality, clinical relevance, and overlap. Seventeen systematic reviews underwent qualitative profiling, of which 11 reported quantitative estimates relevant to the core review-level synthesis. For heart failure hospitalization, the review by Diallo et al. reported HR 0.78 (95% CI 0.73-0.84; n = 25,440). For the composite of cardiovascular death and heart failure hospitalization, Diallo et al. reported HR 0.84 (95% CI 0.78-0.89), Ahmed HM et al. reported HR 0.76 (95% CI 0.64-0.90), and Ahmed M et al. reported RR 0.73 (95% CI 0.57-0.93). Existing reviews also consistently suggested improvements in functional status. The review by Gera et al. reported OR 0.85 (95% CI 0.77-0.93; n = 85,373) for stroke, whereas findings for cardiovascular and all-cause mortality remained inconsistent. Evidence for major adverse cardiovascular events was limited; the review by Gonzales-Uribe et al. reported HR 0.71 (95% CI 0.60-0.86). AMSTAR 2 classified six reviews as having low overall methodological confidence and five as having critically low overall methodological confidence. The CCA was 13.2%, indicating high overlap. All HR, RR, and OR values were estimates reported by included reviews and were not recalculated or quantitatively combined in this umbrella review. At the level of existing evidence syntheses, GLP-1-based therapies appear most consistently associated with fewer heart failure hospitalizations and improved functional capacity in obesity-related HFpEF. However, the review-level evidence does not establish a consistent mortality benefit or support GLP-1-based therapy as a universal mortality-modifying treatment for HFpEF. These agents are better interpreted as emerging metabolic-functional therapies whose apparent benefits must be considered in light of methodological limitations and high overlap among reviews.

PMID 42876799
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