Why can this diabetes drug reverse obesity? Scientists reveal the 'metabolic restart password' of Exenatide peptide
Chapter 1: The dilemma of diabetes treatment and the icebreaker
1. Current situation of global metabolic crisis
1.1Data comparison: diabetes patients increased by 300% in recent 40 years (WHO 2025 report)
From 1985 to 2025: the number of diabetes patients in the world will increase from about 100 million to more than 830 million (an increase of more than 300%), and the number of Chinese patients will reach 233 million (accounting for 22% of the world).
Youthfulness is intensifying: the incidence rate among the 18-29 year old population in China has reached 5%, and it has risen to 6.3% among the 30-39 year old population (less than 2% in 2005).
Economic burden: diabetes related medical expenditure accounts for 12% of the total global health expenditure, with an annual loss of more than one trillion dollars
1.2Traditional treatment bottleneck: The weight gain effect of insulin triggers a "blood glucose obesity" vicious cycle
Weight gain effect:High doses of insulin promote fat synthesis, while hypoglycemia triggers compensatory eating, forming a cycle of "blood sugar drop → weight gain → insulin dosage increase".Research shows that long-term insulin therapy patients gain an average of 2-5 kilograms in weight.
Risk of complications:Obesity exacerbates insulin resistance, forcing dose escalation and increasing the risk of cardiovascular events by 40%.
2.Miracle in Lizard Venom
2.1Discovery process: How the saliva components of the Gila lizard inspired Exenatide peptide synthesis (Harvard research in the 1990s)
This story begins with an off topic scientific exploration - in the early 1990s, endocrinologist John Eng from Harvard Medical School was studying how the venom of the Gila lizard caused severe pain, but accidentally discovered a special protein called exendin-47 while analyzing its components. This discovery has completely changed the pattern of treatment of type II diabetes.
The Inge team found that the structure of exendin-4 is surprisingly similar (52% homology) to human glucagon like peptide-1 (GLP-1), but with a disruptive advantage:
The fatal flaw of GLP-1 in the human body: it is degraded by enzymes within 2 minutes of entering the bloodstream, making it unable to continuously control glucose levels;
The anti sky stability of exendin-4, a venomous lizard, is resistant to enzymatic degradation and has a duration of action exceeding 24 hours.
Like the same 'molecular key', the lizard version is more durable and can repeatedly turn on the insulin secretion switch on cells.
Despite the discovery of a breakthrough, the path of transformation was once blocked:
The cold reception of pharmaceutical giants: Engel lobbied many companies unsuccessfully, because the mainstream research direction of diabetes was insulin analog 7 at that time;
Small company's desperate gamble: In 1995, startup company Amlin took over the patent and synthesized the first exendin-4 analogue - Exenatide 67;
Clinical dramatic verification: Engel's daughter with diabetes became the first group of subjects, and her blood sugar decreased significantly after injection.
2.2Mechanism breakthrough: The world's first GLP-1 analog controls glucose by delaying gastric emptying.
Research shows that GLP-1 has many benefits besides controlling blood sugar. It can reduce the breakdown of liver glycogen, increase the uptake of liver glucose and the synthesis of liver glycogen, increase the breakdown of liver fat, and promote the synthesis of free fatty acids; It can increase cardiac output, reduce hypertension, and protect the myocardium; It can protect and nourish nerves, enhance cognitive function, and reduce the occurrence of neurogenic shock and depression. Research shows that the secretion level of GLP-1 is significantly reduced in patients with type 2 diabetes. In addition to the special glucose control mechanism of GLP-1, it is a new idea for GLP-1 to control the blood glucose in patients with type 2 diabetes.
Chapter 2: The 'Side Effects' of Disrupting Cognition
1. Unexpected gains: weight fluctuations in clinical trials
Key data: BYETURE study shows an average weight loss of 10.2kg over 52 weeks (NEJM 2024)
Mechanism diagram:
graph LR
A [Exenatide activates hypothalamus] -->B [enhances satiety signal]
A -->C [Inhibits NPY neurons in the feeding center]
D [acts on gastrointestinal cells] -->E [GLP-1 receptor activation] -->F [β cell proliferation]
``` ```
2. Triple effect of metabolic reconstruction (referencing 3 mathematical models)
Energy balance equation: ∆ W=k ₁ · GIP - k ₂ · Ghrelin+ε · GLP-1
The core value of metabolic reconstruction ("triple effect" framework)，Metabolic reconstruction integrates multiple omics data through genome scale metabolic models (GEM), and its value can be summarized as:
Technological breakthrough: Building models directly without relying on reference genomes;
Functional analysis: Revealing metabolic diversity and community interactions within species;
Application Empowerment: Personalized Disease Modeling and Metabolic Engineering Optimization.
Chapter 3: Patient Testimony - A Changed Destiny
- Case : From insulin resistance to marathon runners: Exenatide's adjuvant effects and lifestyle changes
Insulin resistance and treatment with Exenatide
Insulin resistance refers to a weakened response of the body to insulin, resulting in a decrease in the efficiency of insulin in promoting glucose uptake and utilization. This situation is usually related to obesity, and Exenatide is a drug commonly used to treat type 2 diabetes, which can help improve insulin sensitivity and thus help control blood sugar level6. Exenatide simulates the action of the intestinal hormone GLP-1, promotes insulin secretion, and inhibits the release of glucagon, thereby reducing blood sugar levels. In addition, Exenatide can also reduce appetite and help patients lose weight, which is very beneficial for improving insulin resistance.
The use of Exenatide and weight loss
According to your description, during the treatment with Exenatide, you successfully lost 45 pounds of weight. This indicates that Exenatide has played a positive role in your treatment process. Exenatide peptide is usually injected once a day, which can help patients control blood sugar and lose weight. In your case, during the 8-month treatment cycle, Exenatide not only helped you control blood sugar, but also significantly reduced weight, which is a crucial step in improving insulin resistance.
Lifestyle transition: from insulin resistance to marathon runners
In addition to medication treatment, lifestyle changes are also key factors in improving insulin resistance and maintaining healthy blood sugar levels. You mentioned becoming a marathon runner, which indicates that you may have increased your physical activity, especially running, during or after Exenatide treatment. Running, as an aerobic exercise, can help increase the body's metabolic rate and reduce fat accumulation, which is beneficial for improving insulin resistance.
Research has shown that endurance exercises such as running can increase serum glucagon levels, which can activate AMPK signaling in pancreatic beta cells and alleviate beta cell aging in insulin resistant mice. This means that exercise not only helps control blood sugar, but may also have a positive impact on the health of pancreatic islet cells. Your experience seems to confirm this point, even after stopping medication for two years, your blood sugar remains stable, which may be the result of a combination of sustained exercise habits and a healthy lifestyle.
Blood glucose stability after discontinuation of medication
You mentioned that after stopping the medication for two years, blood sugar remained stable. This indicates that Exenatide helped you establish a good foundation of blood glucose control during treatment, and subsequent lifestyle changes such as increased exercise and possible dietary adjustments further consolidated this achievement. The improvement of insulin resistance usually requires comprehensive treatment, including medication, dietary control, and exercise. Your situation shows that the combination of these factors can bring long-term health benefits.
Conclusion
From insulin resistance to becoming a marathon runner, your experience demonstrates the effectiveness of Exenatide as a therapeutic tool and the importance of lifestyle changes in maintaining healthy blood sugar levels. Exenatide helps you lose weight and control blood sugar, while consistent exercise habits ensure blood sugar stability after discontinuing the medication. This indicates that for insulin resistant patients, combining drug therapy with a healthy lifestyle can bring significant health improvements and long-term benefits.
Exenatide peptide teaches us that metabolic diseases should not be lifelong cages, but reversible physiological signaling errors. Elena Martinez, Director of Johns Hopkins Metabolic Center.
Martinez's insights mark a shift in metabolic medicine from 'lifelong control' to 'physiological repair'. As she emphasized, "diabetes is not the death of beta cells, but the sleep of beta cells - we have the responsibility to wake them up. This concept is driving individualized reversal strategies to become the new standard
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