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

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Introduction to GLP-1 Receptors

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. Glucagon-like peptide 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. Activation of GLP-1R plays a pivotal role in maintaining glucose homeostasis, appetite regulation, and insulin sensitivity.
Multispan supports GLP-1 research through its GPCR assay development and screening services, tailored for metabolic drug discovery.

Mechanism of Action

This 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 receptor 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.

Therapeutic Applications

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-1R agonist
Obesity or overweight with comorbidities
Novo Nordisk
2021
$7.73 billion (2023)
Zepbound (Tirzepatide)
Dual GLP-1R/GIP receptor agonist
Obesity or overweight with comorbidities
Eli Lilly
2023
$5.2 billion (2023)

GLP-1 Treatments: Results, Side Effects, and Lifestyle Factors

In terms of weight loss in people, GLP-1 drugs 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 of these treatments aim to generate effective therapeutics with fewer and less severe side effects.
For broader insights into related pathways, see our Amylin Family for Drug Discovery, which complements GLP-1-targeted drug development.
While these 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 counterparts.
On the other hand, the benefits of these receptor-targeted therapies 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 therapies for type 2 diabetes and obesity.

Strategies to Bypass Side Effects by Targeting Additional 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 glucagon receptors offer exciting opportunities for treating obesity, diabetes, and even Alzheimer’s, where appetite and metabolic dysfunction play critical roles.
Multispan cell-based assay development services enables dual and multi-receptor profiling.

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-1R 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 dedicated significant effort to developing a robust, HTS-ready cell assay platform and stable cell line clones targeting the GLP-1R family. These assets enable fast, consistent, and reproducible screening of both single and dual agonist compounds, accelerating the discovery of next-generation therapeutics in this pathway.

  • Cell Line Stability

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

  • High Sensitivity

    Optimized to detect subtle changes in receptor 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

See also: MULTISCREENTM Glucagon Cell Assay Products

FAQs

The GLP-1 receptor (GLP-1R) is expressed in the pancreas, gut, brain, and other tissues such as the heart and kidneys. It plays a key role in regulating insulin secretion, appetite, and glucose homeostasis. Because of this, it has become a major target in drug discovery for treating type 2 diabetes and obesity.

GLP-1 receptor agonists work by increasing insulin secretion, inhibiting glucagon release, and slowing gastric emptying. These effects enhance satiety, reduce blood sugar spikes, and promote body weight loss — with clinical results showing up to 15–20% weight loss in individuals using GLP-1 therapies.

Common side effects include gastrointestinal symptoms like nausea, vomiting, diarrhea, and constipation, as well as hypoglycemia and injection site reactions. Ongoing advancements aim to reduce these side effects while preserving therapeutic effectiveness.

Yes. Although most GLP-1 therapies are injectable, oral formulations are being developed to improve patient convenience. As research continues, the absorption and efficacy of oral GLP-1R therapies are expected to improve, offering viable alternatives.

Multispan provides HTS-ready stable cell lines and assay platforms specifically targeting GLP-1R. These tools enable fast, reproducible screening of both single and dual agonist compounds, helping accelerate the development of next-generation metabolic therapies.

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