Microdosing GLP-1s: Does It Work for Weight Loss?
Can tiny doses of powerful GLP-1 drugs help people lose weight or maintain weight loss? Here’s what an obesity doctor has to say about microdosing GLP-1s.
You’ve tried every diet and plan out there. You're curious about medication added to your weight care regimen—maybe this is the boost you needed all along.
For years there’s been a ton of buzz around metformin weight loss. It’s among the most widely prescribed drugs for type 2 diabetes in the United States. However the current hype about the drug isn’t for treating diabetes; it’s the research that shows metformin may help with weight loss too.
Let’s talk about the diabetes piece first. A 2017 editorial in Diabetologia reviewing 60 years of metformin found it was “the eighth most commonly prescribed drug consistently from 2008 to 2012, [with] the number of prescriptions rising from 51.6 million in 2008 to 61.6 million in 2012.” And yet the global health burden of diabetes has increased substantially from 2000 to today. Of the three main kinds of diabetes (type 1, gestational, and type 2), between 90% to 95% of Americans are diagnosed with type 2 diabetes. A person develops type 2 diabetes when their blood sugar is too high, and insulin resistance or a reduced capacity to produce insulin means their body can’t naturally lower their blood sugar levels.
People with type 1 diabetes must treat it with daily insulin. However, those with type 2 diabetes can often manage it with healthy lifestyle changes, like diet and physical activity, diabetes medications, and if needed, insulin therapy.
The diabetes crisis is dire and growing, contributing to 1.5 million deaths in 2019, according to the World Health Organization (WHO). It’s also among the top ten leading causes of death worldwide. But metformin treatment for diabetes management has greatly impacted health care for its ability to help save lives by reducing blood sugar levels.
Metformin has been used clinically since 1957 and was studied from 1960 to 1980 to verify its safety and efficacy in lowering blood glucose levels. It eventually became the “‘optimal’ therapy in type 2 diabetes,” according to the 2017 Diabetologia editorial.
In 1995, the U.S. Food and Drug Administration (FDA) approved metformin to treat type 2 diabetes. And while it's proven to be a very effective diabetes drug over the years, there’s still research being done on metformin weight loss. Here’s what we know now.
Although it’s FDA-approved for diabetes, doctors also prescribe metformin off-label for weight loss. Why? A small placebo-controlled study published in Obesity Research explored the effects of metformin on women with obesity and non-insulin-dependent diabetes mellitus (NIDDM)—meaning people who had diabetes but didn’t need insulin. The study found that the medication also helped reduce body weight.
The 48 participants hadn’t successfully lost weight despite diet therapy. During the metformin trial, they were put on an American Diabetes Association calorie-reduced diet and given 850 mg of metformin or a placebo twice a day.
The clinical trial results were outstanding, and “subjects treated with metformin continue[ed] to lose weight throughout 24 weeks of treatment. Researchers discovered that the medication could trigger feelings of fullness and reduced appetite, reducing calorie intake. After 24 weeks, the average body weight of those on metformin dropped by about 17 pounds compared to the placebo group’s average of just over two pounds—evidence that weight loss is possible on metformin.
A Diabetes Prevention Program Research Group study published in 2012 in Diabetes Care also found metformin weight loss works. In addition, it determined that long-term treatment was safe and helped sustain weight loss for at least ten years. The participants who took metformin—even with no other lifestyle changes— lost the most weight and body fat. However, the placebo group lost no weight, leading researchers to attribute the weight loss success to metformin. According to the study, metformin also “lowers glucose and reduces risk for diabetes in part through weight loss.”
Research points toward metformin as a powerful weight loss tool. After speaking with your Found provider, you may be prescribed metformin for weight loss if you’re a candidate. But prescribing medications is at the medical provider’s discretion, and metformin may not be right for everyone.
We know now metformin helps support weight loss through appetite suppression. A 2019 review published in the Current Obesity Report found that it does this through the gastrointestinal side effects of metformin. In addition, metformin has been shown in studies to “increase secretion of the weight-loss promoting incretin glucagon-like peptide 1 (GLP-1).”
The naturally occurring GLP-1 hormone works in your body by helping to regulate blood sugar levels and control appetite. The term “GLP-1” may ring a bell as you’ve likely heard of popular weight-loss drugs Wegovy®, Victoza®, and Saxenda® that are classified as GLP-1 receptor agonists. These drugs are FDA-approved for weight loss in adults who have obesity or a body mass index (BMI) of 27 or higher with at least one health problem caused by excess weight.
Interestingly, some animal studies suggest metformin may affect pathways in the hypothalamus—an area of the brain that produces hormones that control essential functions like body temperature, heart rate, and hunger. Think of the hypothalamus as the motherboard of a rocket ship controlling all operations, such as destination, gravity, and speed. The hypothalamus ensures we’re in a state of balance or homeostasis; if one small element is off, the ship can go down. And there's also research—in humans—that suggests metformin may alter the parts of our brain tour that affect our food-reward relationship.
It isn’t yet understood how metformin has this effect on the hypothalamus, but researchers continue to seek the link between the two.
As a diabetes drug, metformin may begin to reduce blood glucose levels as soon as two weeks after starting the medication. In regards to weight loss, many studies report weight loss after six months on metformin. However these findings don’t mean one won’t lose a meaningful amount of weight prior to six months—the weight loss will vary from person to person.
Health care providers prescribe metformin in different doses over time. They may also combine it with a GLP-1 medication depending on how your body reacts to the drug. The amount of weight you lose will depend on many factors, including physical activity and exercise.
Remember, your health care provider will prescribe the dose of metformin that’s best for you. Sustainable weight loss isn’t a race. It’s about making small changes daily, so try not to be discouraged if it’s taking longer. You’ll get there.
Metformin may also have other health benefits, including possible cardiovascular health improvement. For example, because it lowers blood sugar, it may lead to reduced risks of heart attack and stroke. A review of studies published in 2017 in Diabetologia noted that while there is a suggestion that metformin is beneficial, “there remains uncertainty about whether it reduces risk of cardiovascular disease among patients with type 2 diabetes.” Research is ongoing.
Another possible health benefit of metformin is that it may ease polycystic ovary syndrome (PCOS) symptoms. This hormonal disorder can cause enlarged ovaries with small cysts and may lead to infertility. Insulin resistance is thought to be a key factor in PCOS development. PCOS isn’t just a reproductive disease either—it may also increase the risk of serious health issues like type 2 diabetes, high blood pressure, and endometrial cancer. Metformin’s ability to lower blood glucose levels may help with insulin resistance in PCOS patients; however, more research is needed.
Metformin also helps with the effects of antipsychotic weight gain. In a 2016 meta-analysis examining 12 studies with a total of 743 patients published in BMC Psychiatry, patients treated with metformin and atypical antipsychotics showed a significant weight loss compared to those patients who took a placebo.
All of this research supports metformin as a valuable therapeutic medication across multiple conditions that can reduce symptoms and aid in treating diseases.
All medications have risk factors. Still, the consensus is that metformin is safe for weight loss, even if you don’t have diabetes. If you experience adverse side effects, they’ll typically lessen within a few weeks. The most common side effects include mild gastrointestinal issues—like diarrhea—but it usually doesn’t outweigh the benefits of using metformin for weight loss.
During the Diabetes Prevention Program Outcomes Study (DPPOS) conducted by the Diabetes Prevention Program Research Group, metformin produced weight loss in participants with obesity and pre-diabetes without significant safety issues.
The authors also noted that “participants reported more gastrointestinal symptoms than placebo participants, however, these abated over time and both types of gastrointestinal symptom reports were similar between groups by the latter years of the DPPOS.”
This suggests that regardless of metformin use, candidates who didn’t even take the medication still experienced stomach issues later in the study.
Various studies have given different doses of metformin before, after, and even with meals. Most commonly, Found health care providers recommend taking it right before bed to prevent any possible nausea or with a meal to avoid an upset stomach. You’ll get personalized guidance on when to take it when you get your subscription. If you’re experiencing symptoms when taking it before a meal, your Found provider may switch up the timing to help alleviate some of those side effects. Following your health care provider’s instructions and listening to your body is important. Also, if you’re prescribed metformin for weight loss, share any feedback so your Found provider can develop the best possible solution for you.
Of course, your metformin dose for weight loss depends entirely on you; your Found health care provider will work with you to develop a plan with thorough vetting. Patients with obesity have been given up to 2,500 mg, which was safe and effective in metformin weight loss efforts. However, as a rule of thumb, you typically begin at a lower dosage level and then steadily increase the dose to determine if it’s working and how well your body tolerates it.
The short and truthful answer is no. The results of taking metformin for weight loss are promising, but physical activity, a healthy diet, and lifestyle changes are fundamental for maintaining your weight-care journey. You may also need to take metformin for an extended period of time to sustain your results and support ongoing weight loss.
Metformin should be combined with behavior and habit changes for long-term weight care for other reasons too. In June 2022, the Endocrine Society announced that a new study found “overweight and obese people maintained an average weight reduction of 10.6% over 3 to 5 years with a program of lifestyle changes combined with anti-obesity medication.”
But how about we pause here in the present? The current research on metformin weight loss is encouraging. The drug helps treat overweight and obesity and is proven safe and effective. All big wins in our book!
Even after reading about metformin weight loss, you may still have a few lingering questions unanswered. We’ve compiled a list of common questions about metformin to help answer those.
Remember, your health care provider is the best person to consult about questions. If you need more answers, please have a conversation with them.
Metformin isn’t a quick-fix for weight loss and isn’t meant to be taken to lose weight fast. Combined with exercise and a healthy diet, metformin can help you lose weight in a sustainable way that’s manageable and meant for long-term weight loss.
The most common side effects of metformin are gastrointestinal issues like diarrhea, nausea, stomach pain, flatulence, and vomiting. Typically these side effects subside after your body gets used to the medication, but if they persist or become unmanageable, let your health care provider know immediately.
Patients typically start on 500 mg or 1,000 mg (500 mg twice a day)—the lowest metformin doses. Those taking metformin for diabetes care combined with insulin will typically begin with a 500 mg dose daily. Your doctor will help you choose the right weight-management dose.
The short answer: no. Hair loss isn’t a known side effect of metformin. But, (yes, there’s a but) metformin can cause a deficiency in vitamin B12 in some patients. When your body lacks enough vitamin B12, it can lead to hair loss.
Talk to your doctor about testing your vitamin levels and tell them if you notice any hair thinning or loss. You may need to take supplements to maintain vitamin levels in your body.
Depending on your dose, the drug's half-life is between four and almost nine hours. If you’ve been using metformin therapeutically, the drug has been found in some people’s blood up to two weeks after they took their last dose, but more commonly, it will stay in your system for about four days.
Taking metformin in the evening can help reduce the risk of experiencing unwanted side effects. Even more, it may help with hyperglycemia (high blood sugar levels) the following morning if you take it at night.
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