GLP-1 Receptor and More: Shaping Obesity Treatment and Metabolic Health

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Understanding the role of GLP-1 Receptor in Drug Discovery

Glucagon-like peptide 1 (GLP-1) is a crucial hormone in the glucagon family, primarily secreted by intestinal L-cells distributed along the gastrointestinal tract. GLP-1 receptor (GLP-1R), on the other hand, is primarily expressed in the pancreas, gut, central nervous system, and also found in other tissues like the heart, kidneys, and lungs. The GLP-1 activation of its receptor plays a pivotal role in maintaining glucose homeostasis appetite regulation, and insulin sensitivity.

The GLP-1 receptor has been an important target in drug development, with successfully FDA-approved treatments for Type 2 diabetes since 2005 and for obesity since 2021. GLP-1 agonists have demonstrated the ability to increase insulin secretion, inhibit glucagon release, and slow gastric emptying, offering powerful benefits in controlling appetite, regulating blood sugar levels, and managing body weight.
The GLP-1 treatments currently approved for commercial use include Liraglutide (Saxenda, Victoza), Semaglutide (Ozempic, Wegovy), and Exenatide (Byetta, Bydureon). The choice of treatment varies depending on the patient’s condition, weight loss goals, side effect profile, cost, and preferred administration method.

FDA-Approved GLP-1R Obesity Medications (As of February, 2025)

Drug Mechanism of Action Indication Company Approval Year Annual Sales (Latest Available)
Wegovy (Semaglutide)
GLP-1 receptor agonist
Obesity or overweight with comorbidities
Novo Nordisk
2021
$7.73 billion (2023)
Zepbound (Tirzepatide)
Dual GLP-1/GIP receptor agonist
Obesity or overweight with comorbidities
Eli Lilly
2023
$5.2 billion (2023)

Exploring the Efficacy of GLP-1 Treatments

In terms of weight loss efficacy, GLP-1 agonists have demonstrated up to a 15-20% weight loss in individuals. In treatment of Type 2 diabetes, these treatments have demonstrated a 5-10% weight loss in patients. This makes GLP-1 agonists an effective approach for both diabetes control and weight management. It is, however, important to consider the side effects of these treatments, which include nausea and vomiting, gastrointestinal issues such as diarrhea and constipation, hypoglycemia, and redness or swelling at the injection site. Continued advancements in GLP-1 treatments aim to generate effective therapeutics with fewer and less severe side effects.
While GLP-1R agonist drugs are typically injected, some patients may desire an alternative method of administering. As research continues to advance, absorption and efficacy of oral GLP-1R therapeutics will improve, potentially offering a comparable alternative to injected GLP-1R agonists.
On the other hand, the benefits of GLP-1 and GLP-1R agonists can also be significantly enhanced through exercise and diet. Regular physical activity, particularly aerobic and resistance training, and fiber-rich diet with healthy fats and lean proteins boost GLP-1 secretion by increasing L-cell sensitivity to nutrients and improving gut motility, enhance satiety, and reduce glycemic excursions. These life-style solutions offer a natural complement to pharmacological GLP-1 therapies for type 2 diabetes and obesity.

Strategies to Bypass Side Effects by Targeting Receptors

To overcome the side effects associated with targeting a single glucagon family receptor, researchers are exploring combination therapies and the possibility of simultaneously targeting other receptors within the glucagon family, such as GIP (Gastric Inhibitory Peptide) receptor to enhance insulin secretion while mitigating the GI side effects of GLP-1R activation alone and Glucagon receptor to reduce glucose production in the liver without exacerbating hyperglycemia. Similarly, secretin, although less studied for weight loss, regulates digestion, fat absorption and digestion, that may provide broader benefits for metabolic therapies. This strategy also extends beyond the incretin receptor family such as Amylin receptors and CB1 (Cannabinoid 1) receptor.
These dual targeting strategies of GLP-1R and other receptors offer exciting opportunities for treating obesity, diabetes, and even Alzheimer’s, where appetite and metabolic dysfunction play critical roles.

Glucagon Receptors in Different Tissues

GLP-1 agonists and other glucagon family receptor targeting drugs possess a wide range of therapeutic and adverse effects depending on the receptor location and receptor role in different tissues. Given the tissue-specific nature of these receptor activation effects, precise targeting of glucagon-family receptors is necessary to provide sufficient treatment for metabolic disease, while also limiting any adverse effects.

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GLP-1R activation in the pancreas enhances the secretion of insulin when elevated levels of blood glucose are present, and when coupled with GIPR activation in the pancreas, which stimulates beta cells to ramp up insulin production, blood sugar can be more effectively regulated in the treatment of Type 2 diabetes.

Glucagon antagonist activity in the liver can help manage hyperglyciemia in diabetes patients by inhibiting glucogenesis and normalizing blood sugar levels.
Common side effects of GLP-1R activation within the gastrointestinal tract also include nausea, vomiting, constipation, and diarrhea, due to the receptor’s role in modulating gastric emptying.
GLP-1R activation in the hypothalamus triggers feelings of fullness, reducing appetite and acting as a powerful food intake modulator for obesity treatments.
Research has also implicated GLP-1R activation in the CNS with neuroprotective effects in Alzheimer’s disease models, but also suggests that neuropsychological symptoms such as depression can be exacerbated through GLP-1R activation.

Multispan GLP-1 Assay-Ready Stable Cell Lines

GLP-1 receptor agonists are among the most promising new drug compounds for highly-effective treatment for widespread metabolic diseases. But without a consistent assay system, the drug discovery timeline can become drastically prolonged, delaying the development of much-needed therapeutics.
Multispan has invested significant amounts of effort in the development of an extensive and robust HTS-ready cell assay platform and stable cell line clones targeting the GLP-1R family. These valuable assets provide a fast, consistent and reproducible assay system for screening for GLP-1R agonist or dual-agonist compound activities in the development of the next generation of GLP-1R agonists.

  • Cell Line Stability

    Stable cell clonality provides consistent expression of GLP-1 and related receptor targets

  • High Sensitivity

    Optimized to detect subtle changes in GLP-1R activity

  • Scalable For HTS

    Our stable cell lines are fully validated to be HTS-ready, making it scalable with unparalleled efficiency

  • No-Wash MULTISCREENTM Assay Kits

    Streamlines experimental procedures by eliminating washing steps found in traditional assays, reducing time-cost and variability. Click here to learn more

  • Detection Of Key Biomarkers

    Our GLP-1 assays can detect various biomarkers involved in GLP-1R signaling, such as cAMP and calcium

MULTISCREENTM Glucagon Cell Assay Products

Receptor FamilyReceptorSpeciesParentalStable Cell Lines Division-Arrested Cells Membranes
GlucagonGHRHhumanHEK293TC1291DC1291MC1291
GIPhumanHEK293TC1290DC1290MC1290
GIPhumanHEK293T β-Arrestin2CA1290DCA1290MCA1290
GIPmouseHEK293TCm1290DCm1290MCm1290
GIPratHEK293TCr1290DCr1290MCr1290
GIPdogHEK293TCd1290DCd1290MCd1290
GIPdogHEK293TCd1290aDCd1290aMCd1290a
GIPrabbitHEK293TCb1290DCb1290MCb1290
GIPpigHEK293TCp1290DCp1290MCp1290
GIPrhesus monkeyHEK293TCpr1290DCpr1290MCpr1290
GIPrhesus monkeyHEK293TCpr1290aDCpr1290aMCpr1290a
GIPferretHEK293TCf1290DCf1290MCf1290
GIPferretHEK293TCf1290aDCf1290aMCf1290a
GLP-1humanHEK293TC1267DC1267MC1267
GLP-1humanCHO-K1C1267-1DC1267-1MC1267-1
GLP-1humanCHO-K1C1267-1aDC1267-1aMC1267-1a
GLP-1humanCHO-K1 β-Arrestin2CA1267-1DCA1267-1MCA1267-1
GLP-1humanHEK293T β-Arrestin2CA1267BA2DCA1267BA2MCA1267BA2
GLP-1cynomolgus monkeyCHO-K1Cpc1267-1DCpc1267-1MCpc1267-1
GLP-1cynomolgus monkeyCHO-K1Cpc1267-1aDCpc1267-1aMCpc1267-1a
GLP-1ratCHO-K1Cr1267-1DCr1267-1MCr1267-1
GLP-1dogCHO-K1Cd1267-1DCd1267-1MCd1267-1
GLP-1dogHEK293TCd1267-1aDCd1267-1aMCd1267-1a
GLP-1mouse CHO-K1Cm1267-1DCm1267-1MCm1267-1
GLP-1mouse CHO-K1Cm1267-1aDCm1267-1aMCm1267-1a
GLP-1pigCHO-K1Cp1267-1DCp1267-1MCp1267-1
GLP-2humanHEK293TC1268DC1268MC1268
GLP-2ratHEK293TCr1268DCr1268MCr1268
GlucagonhumanHEK293TC1266DC1266MC1266
GlucagondogHEK293TCd1266DCd1266MCd1266
GlucagonpigHEK293TCp1266DCp1266MCp1266
GlucagonratHEK293TCr1266DCr1266MCr1266
GlucagonhumanHEK293TC1266ADC1266AMC1266A
GlucagonhumanCHO-K1C1266-1DC1266-1MC1266-1
GlucagonhumanCHO-K1C1266-1aDC1266-1aMC1266-1a
GlucagonhumanCHO-K1 β-Arrestin2CA1266-1DCA1266-1MCA1266-1
Glucagoncynomolgus monkeyCHO-K1Cpc1266-1DCpc1266-1MCpc1266-1
Glucagoncynomolgus monkeyCHO-K1Cpc1266-1aDCpc1266-1aMCpc1266-1a
Glucagoncynomolgus monkeyHEK293TCpc1266DCpc1266MCpc1266
Glucagoncynomolgus monkeyHEK293TCpc1266aDCpc1266aMCpc1266a
SecretinhumanCHO-K1C1228-1DC1228-1MC1228-1

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