Role of GLP-1 in Lipid Metabolism and Weight Loss

Q: What side effects can occur with GLP-1 medications?

GLP-1 receptor agonists, like semaglutide and tirzepatide , are generally well-tolerated, but they can come with some side effects. The more common ones include nausea , vomiting , diarrhoea , constipation , and bloating , particularly during the first few weeks of treatment. These symptoms often ease as your body adapts. Some people might also notice a reduced appetite or mild reactions at the injection site, such as redness or itching. On the rarer side, more serious side effects can occur. These include low blood sugar (especially if used alongside insulin or sulfonylureas), gallbladder issues like gallstones, pancreatitis , or, in very rare cases, thyroid-related issues . There have also been reports of cosmetic changes, such as facial fat loss . If you're thinking about starting GLP-1 therapy, Trimly, a telehealth clinic approved by Singapore's Ministry of Health, offers a tailored, doctor-led approach. Their services include close monitoring for side effects and unlimited follow-ups, ensuring you're supported and safe throughout your weight loss journey.

Q: Why is it important to stay on GLP-1 treatments long-term?

GLP-1 treatments are aimed at addressing obesity as a long-term condition , rather than a short-term fix. Discontinuing the medication often results in regaining the lost weight, which can undo the progress made in areas like metabolic and cardiovascular health. Continuing the treatment helps maintain weight loss and promotes better outcomes for overall metabolic well-being over time. It’s an integral part of a continuous effort to manage weight in a sustainable and effective way.

GLP-1, a hormone produced in your gut, plays a key role in managing blood sugar, appetite, and fat metabolism. It helps regulate insulin, reduces harmful fats, and supports weight loss. For those struggling with obesity or type 2 diabetes, GLP-1 receptor agonists like semaglutide and tirzepatide provide effective solutions by mimicking natural GLP-1 and staying active longer in the body. Clinical trials show these treatments can lead to up to 20% body weight loss, reduce triglycerides, and improve cardiovascular health. However, discontinuing treatment often results in weight regain, highlighting the need for long-term use.

Key takeaways:

GLP-1 reduces appetite, slows digestion, and improves fat metabolism.
Medications like semaglutide and tirzepatide aid weight loss and improve lipid profiles.
Long-term use is necessary for sustained benefits.
Telehealth services in Singapore, such as Trimly, make these treatments accessible, starting at S$350/month.

GLP-1 therapies offer a science-backed approach to addressing obesity and related metabolic challenges.

Role of GLP-1 Receptor Agonists for Weight Loss

How GLP-1 Affects Lipid Metabolism

GLP-1 does more than just regulate blood sugar - it plays a crucial role in how the body processes and stores fats. This is key to its cardiovascular benefits and its ability to aid in weight loss, as it tackles the underlying metabolic issues linked to obesity. Here's how GLP-1 improves insulin sensitivity, encourages fat breakdown, and reduces inflammation.

Improving Insulin Sensitivity

Insulin resistance disrupts the way the body handles glucose and fats. GLP-1 medications help by lowering free fatty acids (FFA) in the blood and increasing adiponectin levels, which are critical for improving insulin sensitivity. Elevated FFAs are a major cause of insulin resistance and pancreatic β-cell dysfunction. By reducing these harmful fats, GLP-1 treatments help restore the body's ability to respond to insulin effectively. The boost in adiponectin further supports healthy fat cells and enhances insulin action.

The STEP-1 trial, conducted in March 2021, highlighted these effects. Among 1,961 adults who took 2.4 mg of semaglutide weekly, participants experienced reductions in triglycerides, VLDL cholesterol, and FFAs, alongside a 14.9% weight loss over 68 weeks.

Increasing Fat Breakdown

GLP-1 doesn’t just improve insulin sensitivity - it also helps the body break down fat. By increasing sympathetic nervous system activity, GLP-1 indirectly promotes lipolysis, which is the breakdown of fat stored in adipose tissue. This process ensures that fat is used as energy instead of being stored.

"GLP-1 indirectly enhances lipolysis via increased sympathetic activity through the central nervous system." - Dr Qiyuan Keith Liu, MedStar Medical Group

Additionally, GLP-1 medications encourage the "browning" of white fat tissue and stimulate thermogenesis in brown fat tissue, which boosts energy expenditure and fat utilisation. In the liver, these medications reduce fat buildup by promoting fatty acid oxidation and lowering VLDL production, which is the main carrier of triglycerides. For example, semaglutide has been shown to reduce triglycerides by up to 15%, while tirzepatide, a dual agonist, achieved reductions as high as 31%.

Reducing Inflammation and Fat Buildup

Excess weight often leads to chronic, low-grade inflammation in fat tissues, which worsens insulin resistance and overall metabolic health. GLP-1 medications counteract this by suppressing proinflammatory molecules like IL-6, TNF-α, and NF-κB. These anti-inflammatory effects occur both through weight loss and through mechanisms that are independent of weight reduction. For instance, clinical trials with semaglutide revealed that only 20% to 60% of the observed decreases in C-reactive protein (CRP) - a marker of inflammation - could be attributed to weight loss and glucose improvements.

Moreover, GLP-1 treatments help prevent the harmful accumulation of fat in non-fat tissues, such as the liver and muscles. This reduction in inflammation and ectopic fat storage contributes significantly to the cardiovascular benefits observed in clinical studies. In the SELECT trial, which concluded in 2023, 17,604 patients with obesity and preexisting cardiovascular disease saw a 20% relative risk reduction in death from cardiovascular causes, nonfatal heart attacks, or strokes over a span of 36 months. These lipid-related benefits highlight the transformative potential of GLP-1 treatments in improving both metabolic and cardiovascular health.

Clinical Studies on GLP-1 and Weight Loss

Clinical trials have consistently shown that GLP-1 treatments not only influence lipid metabolism but also lead to meaningful and lasting weight loss.

SCALE Trial (Liraglutide)

The SCALE trial revealed that participants taking liraglutide 3.0 mg experienced an average weight loss of 8.4 kg (8.0% of body weight) over 56 weeks, compared to 2.8 kg (2.6%) in the placebo group. Additionally, 63.2% of those on liraglutide achieved at least a 5% reduction in body weight, while 33.1% shed more than 10% of their initial weight. Beyond weight loss, the treatment improved fasting lipid levels, with reductions in total cholesterol and triglycerides. Most gastrointestinal side effects were temporary and occurred mainly within the first 4 to 8 weeks.

"Weight loss with liraglutide is dose-dependent up to 3.0 mg once daily and is mediated by reduced appetite and energy intake rather than by increased energy expenditure." - New England Journal of Medicine

These findings set the stage for larger studies that further examined the cardiovascular and metabolic benefits of GLP-1 therapies.

SELECT Trial (Semaglutide)

SELECT Trial

Between October 2018 and March 2021, the SELECT trial enrolled 17,604 participants aged 45 and above, all with a BMI of 27 or higher and established cardiovascular disease but no diabetes. Over an average of 39.8 months, participants received weekly doses of semaglutide (2.4 mg) or placebo. Results showed that semaglutide reduced the risk of major adverse cardiovascular events - such as death from cardiovascular causes, nonfatal heart attacks, or strokes - by 20%.

Weight loss was also sustained, with semaglutide users maintaining a mean weight reduction of 10.2% at 208 weeks, compared to 1.5% in the placebo group. Improvements in lipid profiles were notable: triglycerides decreased by 18.34%, HDL cholesterol increased by 4.86%, and high-sensitivity C-reactive protein levels dropped by 39.12%, compared to just 2.08% in the placebo group. By week 104, 52.4% of participants improved their BMI category, and 12% achieved a healthy BMI below 25 kg/m².

Building on these successes, researchers have begun exploring the potential of dual receptor agonists for even greater metabolic outcomes.

Recent Research on Dual Agonists

Recent studies have investigated dual agonists targeting both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors. This dual mechanism enhances fat breakdown and improves overall metabolic regulation. In May 2025, the SURMOUNT-5 trial compared tirzepatide - a dual GLP-1/GIP agonist - with semaglutide in 751 adults with obesity. Over 72 weeks, tirzepatide delivered an average weight loss of 20.2%, compared to 13.7% for semaglutide. Waist circumference reductions were also more pronounced, with decreases of 18.4 cm for tirzepatide versus 13.0 cm for semaglutide.

The SURMOUNT-1 trial focused on 2,539 obese adults without diabetes. Participants receiving 15 mg of tirzepatide weekly for 72 weeks achieved a mean weight reduction of 20.9% (23.6 kg), compared to 3.1% (2.4 kg) with placebo. Total body fat mass decreased by 33.9% with tirzepatide, compared to 8.2% in the placebo group. Triglycerides dropped by 20.3 percentage points more than placebo, HDL cholesterol rose by 8.0%, and an impressive 95.3% of participants with prediabetes returned to normal blood sugar levels.

Notably, tirzepatide has been shown to lower triglycerides by up to 31%, nearly doubling the reduction achieved by semaglutide.

What to Expect: GLP-1 Results Over Time

GLP-1 Weight Loss Timeline: What to Expect Over 12 Months

GLP-1 treatments deliver gradual changes, building momentum over time. By understanding the different phases, you can set realistic goals and stay motivated throughout your weight loss journey.

1-3 Months: Early Changes

Treatment typically starts with a low dose to minimise gastrointestinal discomfort. While you may notice some effects within the first week, the full impact usually unfolds by weeks 8 to 12.

"It takes about 8 to 12 weeks of treatment with a GLP-1 RA to start seeing the full effect." - NOVI Team

During this phase, many experience reduced food cravings and greater satiety as early as the first week. Weight loss typically ranges from 2.3 to 6.8 kg in the initial weeks, with water weight shedding first (weeks 1–2) and fat loss becoming more prominent by weeks 3–4. Clinical studies reveal a 21.64% reduction in visceral fat area and a 14.20% decrease in total body fat by the three-month mark. Even fat surrounding the heart, known as epicardial adipose tissue, decreases by 20% within 12 weeks.

To support your progress, focus on 80 to 120 grams of protein daily to protect muscle mass and drink 8 to 10 glasses of water each day to stay hydrated. Most initial side effects, like gastrointestinal issues, tend to subside after four to six weeks as your body adapts.

These early changes set the stage for continued improvements in the months ahead.

3-6 Months: Continued Progress

Between the third and sixth months, you’ll likely shift to a maintenance dose, which often brings more noticeable results. On average, individuals lose an additional 5 to 8 kg during this period, which can significantly improve cholesterol levels - lowering LDL by 5 mg/dL and increasing HDL by 3 mg/dL.

Certain groups, such as younger individuals, women, those without diabetes, and people with a higher starting weight, tend to see even better results during this phase. These changes not only help with weight management but also improve metabolic health, particularly by addressing lipid markers and reducing cardiovascular risks.

As you continue treatment, these benefits evolve into long-term, sustainable outcomes.

6-12 Months and Beyond: Long-Term Benefits

Long-term use of GLP-1 treatments sustains weight loss, with studies showing a 10.2% reduction in body weight at 208 weeks. Waist circumference decreases by an average of 7.7 cm, and over half of users experience improved BMI by week 104. The SELECT trial, which followed 17,604 adults over four years, found that participants on semaglutide maintained these results, compared to just a 1.5% weight reduction in the placebo group.

"Weight loss was sustained over 4 years." - Nature Medicine

The cardiovascular benefits are equally noteworthy. Semaglutide has been shown to reduce the risk of major cardiovascular events - such as heart attacks, strokes, and cardiovascular-related deaths - by 20% over four years. Additionally, markers of systemic inflammation, like C-reactive protein, remain lower, and blood pressure improvements persist.

Weight loss generally continues up to week 65 before stabilising into a maintenance phase. However, it’s important to note that these benefits rely on ongoing treatment. In the STEP 1 trial, participants who discontinued semaglutide regained two-thirds of their previous weight loss within a year. This highlights the importance of long-term commitment to GLP-1 therapies to achieve lasting improvements in weight and metabolic health.

GLP-1 Treatment Through Telehealth

With strong clinical backing, telehealth has made accessing GLP-1 treatments easier and more timely, bringing the benefits of these medications to more people.

Why GLP-1 Medications Work for Weight Loss

GLP-1 medications are effective for weight loss because they address both metabolic and behavioural factors. Studies show that up to 80% of a person’s weight is influenced by biological and health-related factors, rather than sheer willpower. These medications mimic natural hormones responsible for regulating appetite and feelings of fullness. For individuals with obesity, these hormones are often at lower levels, which can lead to overeating. By addressing these hormonal imbalances, GLP-1 medications help remove one of the key barriers to achieving long-term weight loss.

Acacia Parks, PhD, Fractional Chief Science Officer at Found, describes the experience of using GLP-1 medications:

"The experience of using a GLP-1 has been like systematically peeling away behaviour patterns that I thought were part of me, part of my personality. They were actually hormonal signals insisting, begging me not to weigh less than my body thought I should."

Personalised GLP-1 Treatment with Trimly

Trimly

In Singapore, MOH-approved telehealth services like Trimly make GLP-1 treatments accessible by removing obstacles like distance, time, and high costs. Through Trimly, consultations are conducted online, and medications are delivered straight to your doorstep.

Trimly offers both oral and injectable GLP-1 options, starting at S$350 per month. Their approach is personalised, with doctor-led treatment plans tailored to your health needs and weight-loss goals. The service also includes unlimited free follow-ups, allowing doctors to monitor your progress, manage any side effects, and adjust dosages as necessary. This ensures that your treatment remains safe and effective throughout your weight-loss journey.

Before starting your treatment, it’s important to confirm that your telehealth provider is licensed by the Ministry of Health. You can check this via the HealthHub directory. To prepare for your teleconsultation, gather your medical history, including details about current medications, allergies, and recent treatments. Make sure you’re in a quiet, well-lit space for the video call. These streamlined services make GLP-1 treatment more accessible, supporting sustainable and effective weight loss.

Conclusion

GLP-1 receptor agonists have shown impressive results in addressing obesity and metabolic dysfunction by targeting the biological factors at the heart of these conditions. Rather than merely managing symptoms, these treatments aim to tackle the root causes, offering a more effective approach.

Clinical trials have demonstrated notable benefits, including improved cardiovascular health and significant weight loss. However, it’s important to note that discontinuing these treatments may lead to regaining up to two-thirds of the lost weight within a year, underscoring the chronic nature of obesity. This evidence shapes current clinical practices in Singapore and highlights the importance of sustained care.

For Singaporeans exploring effective weight loss options, combining GLP-1 medications with tailored lifestyle changes can offer a comprehensive solution. Services like Trimly provide MOH-approved, doctor-supervised care with personalised dosing, unlimited follow-ups, and convenient home delivery. These features are designed to help individuals achieve and maintain better metabolic health over the long term.

Consider exploring GLP-1 treatments for a safe and effective path to lasting weight loss.

FAQs

How do GLP-1 medications support weight loss and improve metabolic health?

GLP-1 (glucagon-like peptide-1) medications play a significant role in weight loss by addressing key processes in the body. They work by activating the brain's satiety centres, making you feel full sooner, and by slowing down how quickly your stomach empties. Together, these effects help curb hunger and reduce overall calorie consumption, paving the way for healthier eating habits over time.

Beyond weight management, GLP-1 helps regulate blood sugar levels. It does this by increasing insulin production while lowering glucagon levels, but only when glucose levels are elevated, minimising the risk of sudden blood sugar spikes. Additionally, it aids fat metabolism by encouraging fat breakdown and limiting fat storage, which can lead to better lipid profiles and reductions in visceral fat.

In Singapore, Trimly provides access to GLP-1 medications - both oral and injectable - through its online telehealth platform. With tailored treatment plans and unlimited virtual consultations, Trimly ensures a supportive, science-backed approach to achieving long-term weight loss and improved metabolic health.

What side effects can occur with GLP-1 medications?

GLP-1 receptor agonists, like semaglutide and tirzepatide, are generally well-tolerated, but they can come with some side effects. The more common ones include nausea, vomiting, diarrhoea, constipation, and bloating, particularly during the first few weeks of treatment. These symptoms often ease as your body adapts. Some people might also notice a reduced appetite or mild reactions at the injection site, such as redness or itching.

On the rarer side, more serious side effects can occur. These include low blood sugar (especially if used alongside insulin or sulfonylureas), gallbladder issues like gallstones, pancreatitis, or, in very rare cases, thyroid-related issues. There have also been reports of cosmetic changes, such as facial fat loss.

If you're thinking about starting GLP-1 therapy, Trimly, a telehealth clinic approved by Singapore's Ministry of Health, offers a tailored, doctor-led approach. Their services include close monitoring for side effects and unlimited follow-ups, ensuring you're supported and safe throughout your weight loss journey.

Why is it important to stay on GLP-1 treatments long-term?

GLP-1 treatments are aimed at addressing obesity as a long-term condition, rather than a short-term fix. Discontinuing the medication often results in regaining the lost weight, which can undo the progress made in areas like metabolic and cardiovascular health.

Continuing the treatment helps maintain weight loss and promotes better outcomes for overall metabolic well-being over time. It’s an integral part of a continuous effort to manage weight in a sustainable and effective way.