Metformin for Weight Loss: Uses, Dosage, and Results (2025)

Metformin is the most commonly prescribed medication for type 2 diabetes, but it is increasingly being used off-label for weight loss. This comprehensive guide explores the clinical evidence, mechanisms of weight loss, typical results, dosing strategies, and how metformin compares to newer GLP-1 agonist medications for weight management.

What is Metformin and How Does It Work?

Metformin is a biguanide class medication that has been used for diabetes management for over 60 years. It works through multiple mechanisms to improve blood glucose control and support weight loss. Unlike insulin-stimulating medications, metformin does not cause weight gain and may actually promote weight loss in many patients, making it unique among diabetes drugs.

The primary mechanism of metformin involves improving insulin sensitivity, which is the ability of your cells to respond to insulin effectively. In type 2 diabetes and obesity, cells become resistant to insulin, forcing the pancreas to produce excess insulin to push glucose into cells. This high insulin state promotes fat storage and makes weight loss difficult. Metformin reduces insulin resistance, allowing the body to use less insulin overall. Lower insulin levels make it easier for the body to access stored fat for energy.

Metformin activates an enzyme called AMPK (AMP-activated protein kinase), often called the body\'s metabolic master switch. When AMPK is activated, it increases cellular energy production, enhances mitochondrial function, and increases fat oxidation. This activation occurs primarily in muscle cells and liver cells, the two largest consumers of glucose in the body. By improving glucose utilization in these tissues, metformin reduces blood sugar spikes after meals and decreases the amount of glucose that gets converted to fat.

The medication also affects the liver\'s glucose production. People with insulin resistance overproduce glucose from the liver, which contributes to high fasting blood sugar levels. Metformin suppresses hepatic glucose production, reducing fasting glucose by 20-30% in most patients. This effect is crucial for weight loss because excessive glucose production drives cravings and energy crashes that trigger overeating.

Additionally, metformin may alter the composition of gut bacteria. The microbiome influences metabolism, appetite signaling, and energy harvest from food. Metformin appears to promote growth of beneficial bacteria while reducing harmful species. These changes may contribute to modest appetite reduction and improved metabolic efficiency. The accumulated effect of improved insulin sensitivity, increased fat burning, altered glucose metabolism, and microbiome changes produces meaningful weight loss, particularly when combined with dietary modifications and exercise.

The Diabetes Prevention Program Trial: Landmark Evidence

The Diabetes Prevention Program (DPP) is the most significant clinical trial demonstrating metformin\'s weight loss effects. Conducted from 1996 to 2001, this landmark study enrolled over 3,200 overweight or obese people with prediabetes (fasting glucose between 95-125 mg/dL). The study compared three approaches: lifestyle modification alone, metformin plus standard lifestyle advice, and placebo plus standard lifestyle advice.

The lifestyle modification group, which included intensive diet counseling, exercise recommendations, and behavioral coaching, achieved an average weight loss of 7% of body weight (approximately 15 lbs for a 200 lb person) over the first year, with most weight remaining off during the subsequent 2.8-year follow-up period. This group had the best outcomes, reducing diabetes incidence by 58%.

The metformin group, receiving 1,000 mg twice daily (2,000 mg total daily dose) plus standard lifestyle advice, achieved an average weight loss of 2.7% of body weight (approximately 5-6 lbs for a 200 lb person) during the first year. This weight loss was less dramatic than intensive lifestyle modification but still clinically meaningful. Importantly, the metformin group maintained most of this weight loss throughout the study. Metformin reduced the diabetes incidence by 31%, or about half as effectively as intensive lifestyle modification.

The key insight from the DPP was that metformin alone is not as effective as intensive lifestyle modification, but it provides meaningful benefit with much less effort. For patients who struggle with the intensity of lifestyle changes or cannot access intensive lifestyle programs, metformin offers a practical medication-based approach to preventing diabetes and achieving modest weight loss.

The DPP also revealed important information about which patients benefited most from metformin. Younger patients (age < 45) and those with higher baseline BMI achieved the greatest weight loss with metformin. Older patients (age > 60) and those with normal weight at baseline showed minimal metformin benefit. This suggests metformin is most effective for younger, overweight individuals with insulin resistance.

Weight Loss Mechanisms: AMPK Activation and Beyond

Understanding the specific mechanisms by which metformin causes weight loss helps explain why results are modest compared to GLP-1 agonists and why lifestyle modifications remain crucial for optimizing results. The primary mechanism, AMPK activation, deserves detailed explanation.

AMPK is a protein kinase that functions as a cellular energy sensor. When cells have adequate energy (ATP is plentiful), AMPK remains inactive. When energy is low (AMP accumulates), AMPK activates. This activation triggers multiple metabolic adjustments that increase energy production and reduce energy expenditure on non-essential processes. In simple terms, AMPK causes your cells to become more efficient at producing and using energy.

When metformin activates AMPK, several metabolic changes occur simultaneously. First, fat oxidation increases in muscle cells and liver, meaning the body burns more stored fat for energy. Second, glucose utilization improves, reducing the amount of glucose that gets converted to fat and stored. Third, mitochondrial function improves, meaning cells produce more energy (ATP) from the same amount of fuel, reducing the caloric excess that would be stored as fat. Fourth, protein synthesis and cellular growth processes slow slightly, reducing the metabolic demand for excessive calorie consumption.

Beyond AMPK activation, metformin improves insulin sensitivity through multiple pathways. In the muscles, metformin increases glucose transporter expression, allowing muscles to take up glucose more efficiently without requiring excessive insulin. In the liver, metformin reduces the activity of enzymes involved in glucose production, decreasing the amount of glucose your liver manufactures. In fat cells, metformin improves insulin signaling while reducing inflammation, helping fat cells function more normally and less likely to expand.

The improvement in insulin sensitivity has profound implications for weight management. Insulin is a powerful storage hormone. When insulin levels are high (as in insulin resistance), the body preferentially stores nutrients as fat and actively resists using stored fat for energy. Metformin, by reducing insulin levels, shifts the body from a storage-oriented state to a fat-burning state. This shift is subtle compared to the dramatic appetite suppression from GLP-1 agonists but meaningful over months.

Typical Weight Loss Results and Timeline

Based on clinical trials and real-world clinical practice, metformin produces consistent but modest weight loss. Understanding the typical timeline and magnitude of results helps set appropriate expectations and maintain motivation during treatment.

Weeks 1-4: Most patients experience minimal weight loss during the first month (0-2 lbs). However, gastrointestinal side effects are most prominent during this period. Weight change during this phase is often related to water loss and reduced food intake due to GI distress. Some patients actually gain weight temporarily if GI upset causes them to eat high-calorie foods that are easier to tolerate.

Weeks 4-12: Weight loss accelerates to 0.5-1.5 lbs per week as the gastrointestinal side effects diminish and the metabolic effects of metformin become more pronounced. By the 12-week mark, most patients have lost 2-6 lbs. This is the period where the medication\'s appetite-stabilizing effects become noticeable, and patients report fewer cravings and more stable energy levels throughout the day.

Months 3-6: Weight loss continues at 0.25-0.75 lbs per week, with cumulative loss of 5-10 lbs by month 6. Many patients reach their maximum weight loss around the 6-month mark. The rate of loss decelerates as the body adapts to the medication and approaches a new equilibrium. Patients who combine metformin with deliberate dietary changes lose at the higher end of this range, while those relying on metformin alone lose at the lower end.

Months 6-12: Weight loss plateaus significantly. Many patients experience weight stability despite continued medication, while others lose an additional 1-2 lbs through continued adherence to dietary changes. Some patients gradually regain weight even while continuing metformin, particularly if they relax their dietary discipline.

Beyond 12 months: Long-term weight loss is variable. Some patients maintain their reduced weight indefinitely with metformin plus lifestyle modifications. Others gradually regain weight despite continued medication. The key determinant of long-term success is whether the dietary and exercise changes that supported initial weight loss become permanent lifestyle modifications or temporary changes that reverse over time.

Metformin Dosage for Weight Loss

The typical metformin dosage for weight loss ranges from 500 mg to 2,000 mg daily, divided into multiple doses. The dosing approach depends on the formulation used, side effect tolerance, and desired effects.

Immediate-release metformin is typically dosed at 500 mg one to three times daily, for a total of 500-1,500 mg daily. The starting dose is usually 500 mg once daily with dinner, the meal associated with the largest metabolic benefit. This starting dose minimizes gastrointestinal side effects. The dose increases gradually: 500 mg twice daily after 1-2 weeks, then 500 mg three times daily after another 1-2 weeks. The typical therapeutic dose for weight loss is 1,000-1,500 mg daily (500 mg with lunch and dinner, or 500 mg with three meals).

Extended-release metformin is dosed once daily, typically in the evening. The starting dose is 500 mg once daily, increasing to 1,000 mg, then 1,500-2,000 mg after 1-2 weeks at each dose level. Extended-release formulations cause fewer gastrointestinal side effects than immediate-release versions because the medication is absorbed more slowly and steadily. Many patients tolerate higher doses of extended-release metformin (up to 2,000 mg daily) with minimal GI distress.

The maximum recommended dose is 2,000-2,500 mg daily, though most patients achieve weight loss benefits with 1,000-1,500 mg daily. Doses above 2,000 mg daily do not produce proportionally greater weight loss and increase the risk of side effects. Kidney function must be adequate for higher doses; patients with creatinine clearance < 45 mL/min should not exceed 1,000 mg daily.

The timing of doses can influence effectiveness. Taking metformin with meals, particularly larger meals, maximizes the metabolic benefit and minimizes gastrointestinal side effects. Some evidence suggests taking metformin with your largest meal of the day produces the best results. Taking metformin with food reduces nausea by 25-30% compared to taking it on an empty stomach.

Duration of treatment for weight loss is typically indefinite or until weight loss goals are achieved and lifestyle changes are established. Some patients take metformin for 6-12 months for weight loss, then discontinue it if lifestyle changes are sufficiently established to maintain weight. Others take metformin long-term for prevention of diabetes or cardiovascular disease, with weight loss as an additional benefit.

Metformin vs. Extended-Release: Which Formulation?

Two primary formulations of metformin are available: immediate-release (IR) and extended-release (XR or ER). Both contain the same active ingredient but differ in how quickly the drug is absorbed and how long it remains active in your system.

Immediate-release metformin reaches peak blood levels within 1-3 hours and is excreted relatively quickly. This formulation is usually dosed two to three times daily. The advantage is that peak drug levels are higher, which may produce more robust AMPK activation and metabolic effects. The disadvantage is that blood levels fluctuate throughout the day, and gastrointestinal side effects are more common and more severe.

Extended-release metformin is absorbed slowly over 4-8 hours, producing steady, consistent drug levels throughout the day and night. This formulation is dosed once daily, usually in the evening. The primary advantage is significantly fewer gastrointestinal side effects; some patients who cannot tolerate immediate-release metformin due to diarrhea or nausea tolerate extended-release well. The secondary advantage is better adherence because once-daily dosing is easier to remember and incorporate into daily routines.

For weight loss specifically, the choice between formulations should be based on side effect tolerance and adherence. If you experience gastrointestinal side effects with immediate-release metformin, switching to extended-release often resolves the problems while maintaining weight loss benefits. If you achieve good tolerability with immediate-release metformin, no need to switch. Extended-release formulations are generally preferred for long-term weight management because better tolerability leads to better adherence.

Generic formulations of both immediate and extended-release metformin are available and significantly cheaper than branded versions (Glucophage, Glucophage XR). Generic metformin is chemically identical and produces identical results. The extended-release generic formulations are particularly cost-effective and well-tolerated.

Side Effects and Safety Considerations

Metformin is generally well-tolerated, with side effects that are usually mild to moderate and often resolve with time or dose adjustment. Understanding potential side effects helps you manage them effectively and decide if metformin is appropriate for your situation.

Gastrointestinal side effects are the most common, affecting 25-30% of patients starting metformin. Diarrhea is the most frequent complaint, occurring in 10-15% of users, particularly with immediate-release formulations. Nausea affects 5-10% of patients, usually during the first week of treatment. Vomiting, abdominal cramping, and flatulence affect smaller percentages of patients. These side effects are almost always most severe during the first 1-2 weeks and diminish significantly as your body adapts.

Strategies to minimize gastrointestinal side effects include: taking metformin with food, starting with lower doses and increasing gradually, switching from immediate-release to extended-release formulation, reducing dose if side effects are severe, and ensuring adequate hydration. Certain probiotic supplements and soluble fiber (psyllium) may also reduce diarrhea in some patients. If gastrointestinal side effects persist beyond 2-3 weeks despite these strategies, they may not resolve and metformin may not be suitable.

Vitamin B12 deficiency develops in 10-30% of patients taking metformin long-term (more than 1 year). Metformin reduces B12 absorption by interfering with calcium-dependent B12 uptake in the terminal ileum. Symptoms include fatigue, numbness or tingling in fingers and toes, weakness, memory problems, and difficulty concentrating. You should have B12 levels checked before starting metformin and annually while taking it. If deficiency develops, vitamin B12 supplementation (typically 1,000 mg intramuscularly monthly or oral supplements) reverses the deficiency and symptoms.

Less common side effects include metallic taste in the mouth, headaches, muscle pain, and skin reactions. These effects are minor and rarely warrant discontinuing the medication. Serious side effects like lactic acidosis (buildup of lactate in the blood) are extremely rare, occurring in 3-10 per million patient-years, almost exclusively in patients with severe kidney disease, liver disease, or acute illness. Patients with normal kidney and liver function have minimal risk.

Contraindications to metformin include severe kidney disease (eGFR < 30 mL/min), acute liver disease or cirrhosis, acute illness or sepsis, and scheduled procedures with contrast dye (must be temporarily stopped). Metformin should be used cautiously in patients with moderate kidney disease (eGFR 30-45). Patients over age 65 should have kidney function monitored more frequently because kidney function naturally declines with age.

Metformin and Vitamin B12: Prevention and Management

The B12 deficiency associated with metformin use warrants special attention because it can develop insidiously without obvious symptoms until deficiency is severe. Understanding the mechanisms and prevention strategies helps minimize this risk.

Metformin reduces B12 absorption by decreasing intrinsic factor production and altering calcium-dependent B12 uptake in the intestines. This effect occurs in approximately 10-30% of metformin users, with higher rates in those taking higher doses (above 2,000 mg daily) or taking metformin for longer periods (more than 5 years). B12 deficiency develops slowly because your liver stores 2-5 years\' worth of B12, so symptoms may not appear until stores are nearly depleted.

High-risk patients for B12 deficiency include those over age 60 (absorption naturally declines with age), patients with gastrointestinal disease (Crohn\'s, celiac disease, pernicious anemia), vegetarians or vegans (dietary B12 sources are limited), and those taking other medications that reduce B12 absorption (like certain gastric acid-reducing medications).

Prevention strategies include baseline B12 testing before starting metformin, annual B12 testing while taking metformin, dietary focus on B12-rich foods (meat, fish, eggs, dairy) for non-vegetarians, and proactive supplementation in high-risk patients. Some providers recommend routine B12 supplementation (1,000 mcg monthly or 2,000 mcg daily orally) for all patients taking metformin long-term, though this is not universal practice.

If deficiency is detected, B12 can be supplemented orally (1,000-2,000 mcg daily) or intramuscularly (1,000 mcg monthly). Intramuscular injections bypass the absorption problems caused by metformin and are often preferred for treating established deficiency. Once normal levels are restored, ongoing supplementation prevents recurrence.

Drug Interactions and Cautions

Metformin has relatively few significant drug interactions compared to many medications, but several important ones warrant attention. Understanding potential interactions helps ensure safe and effective use.

Contrast dye used in certain imaging procedures (CT scans with iodinated contrast, angiograms) can temporarily impair kidney function, increasing the risk of lactic acidosis if metformin continues. Standard practice is to stop metformin at the time of the procedure and not resume until 48 hours after the procedure, once kidney function is confirmed to be normal. This is a precaution; true lactic acidosis from contrast is uncommon in healthy patients.

Medications that reduce kidney function (ACE inhibitors, NSAIDs, diuretics) may increase metformin accumulation and toxicity risk. Kidney function should be monitored more frequently in patients taking these combinations. Elderly patients on these combinations warrant particularly close monitoring.

Alcohol can increase the risk of lactic acidosis, particularly heavy alcohol consumption. Moderate alcohol consumption is generally considered safe, but heavy drinkers should consider this risk when taking metformin.

Certain medications like cimetidine (an acid-reducing agent) and some antibiotics compete with metformin for kidney excretion, potentially increasing metformin levels. These combinations usually require no adjustment but warrant awareness.

Metformin itself does not typically interact with other weight loss medications. Many patients take metformin plus other drugs like orlistat or GLP-1 agonists without problems. In fact, combining metformin with GLP-1 agonists can produce additive metabolic benefits, though weight loss is primarily driven by the GLP-1 effect.

Metformin vs. GLP-1 Agonists: Comparative Effectiveness

The landscape of weight loss medications has expanded dramatically with the advent of GLP-1 receptor agonists like semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound). Understanding how metformin compares helps determine which medication or combination is most appropriate for your situation.

Weight loss magnitude is the most obvious difference. Metformin produces weight loss of 5-10 lbs (2-4% of body weight), while GLP-1 agonists produce 30-50+ lbs (15-22% of body weight). This represents a three-to-five-fold difference in weight loss effectiveness. For patients seeking significant weight loss, GLP-1 agonists are substantially superior.

However, several factors favor metformin for certain patients. Cost is dramatically lower; generic metformin costs $10-30 monthly, while GLP-1 agonists cost $300-1,000+ monthly even with insurance. Metformin requires no injections, while GLP-1 agonists require weekly injections. Metformin has been used for 60+ years with extensive long-term safety data, while GLP-1 agonists for weight loss have only 2-3 years of extensive use data. Metformin improves insulin sensitivity and metabolic health even independent of weight loss, benefits that persist beyond weight loss goals. GLP-1 agonists are primarily appetite suppressants without the metabolic improvements.

Side effect profiles differ significantly. Metformin causes mainly gastrointestinal effects in a minority of patients, which resolve quickly. GLP-1 agonists cause nausea and gastrointestinal effects in 25-40% of users, which can be severe and persistent. Additionally, GLP-1 agonists carry concerns about muscle loss during rapid weight loss, while metformin combined with resistance training preserves muscle better.

Ideal candidates for metformin include: patients with prediabetes or type 2 diabetes (dual benefit of metabolic improvement and weight loss), patients seeking modest weight loss (5-15 lbs), budget-conscious patients, those with needle phobia, and patients prioritizing long-term safety data. Ideal candidates for GLP-1 agonists include: patients seeking dramatic weight loss (30+ lbs), those with obesity-related health conditions (severe sleep apnea, joint problems), patients who can afford the high cost, and those willing to tolerate injection protocols and potential side effects.

Combination therapy with metformin plus GLP-1 agonist is sometimes used and can be particularly effective for patients with type 2 diabetes seeking substantial weight loss. The metformin improves insulin sensitivity while the GLP-1 agonist suppresses appetite, producing greater overall metabolic improvement than either drug alone. However, weight loss is primarily driven by the GLP-1 agonist; metformin doesn\'t substantially amplify GLP-1 weight loss effects beyond the metformin effect alone.

Who Benefits Most from Metformin for Weight Loss?

While metformin can support weight loss in many people, certain individuals are ideal candidates and likely to achieve the best results. Understanding if you fit this profile helps set realistic expectations.

Patients with prediabetes or type 2 diabetes are the best candidates for metformin for weight loss. The medication addresses two goals simultaneously: blood sugar control and weight loss. The Diabetes Prevention Program confirmed that metformin particularly benefits younger (age < 45), overweight (BMI 25-35) people with elevated fasting glucose or impaired glucose tolerance. If you have a fasting glucose of 100-125 mg/dL, an HbA1c of 5.7-6.4%, or a family history of diabetes, metformin offers significant preventive benefit beyond weight loss.

Patients with insulin resistance but normal glucose tolerance may also benefit from metformin, though it\'s less commonly prescribed for this indication. Symptoms suggesting insulin resistance include: difficulty losing weight despite low calorie intake, energy crashes after eating carbohydrates, strong carbohydrate cravings, history of gestational diabetes, and polycystic ovary syndrome (PCOS). A fasting insulin level > 10-12 mIU/L (with normal fasting glucose) confirms insulin resistance.

Patients who cannot tolerate or afford GLP-1 agonists represent another important group. Metformin is an effective alternative for those unable to use semaglutide or tirzepatide due to cost, side effects, or other medical reasons. While metformin produces less weight loss, modest improvement is better than no treatment.

Patients with polycystic ovary syndrome (PCOS) benefit particularly from metformin. PCOS is characterized by insulin resistance and irregular ovulation. Metformin improves insulin sensitivity, which normalizes ovulation and hormone levels in many PCOS patients, in addition to supporting modest weight loss. Many gynecologists prescribe metformin specifically for PCOS management.

Conversely, patients who are unlikely to benefit include: those with normal insulin sensitivity and normal glucose tolerance (no insulin resistance), those seeking rapid or dramatic weight loss (they need GLP-1 agonists), and those with severe kidney disease (metformin is contraindicated). Additionally, some individuals simply don\'t respond to metformin; approximately 20-30% of patients taking metformin experience minimal weight loss despite compliance. If you don\'t see meaningful progress after 4-6 months, metformin may not work well for you.

Lifestyle Modifications Maximize Metformin Results

The landmark Diabetes Prevention Program showed that intensive lifestyle modification alone produced superior weight loss compared to metformin alone. However, combining metformin with dietary changes and exercise produces better results than metformin alone. To maximize results, lifestyle modifications are essential.

Dietary modifications should focus on reducing calorie intake while improving food quality. Reduce refined carbohydrates, added sugars, and ultra-processed foods, as these trigger blood sugar spikes that perpetuate insulin resistance and cravings. Replace these with whole grains, legumes, vegetables, and fruits. Increase protein intake to 0.8-1 gram per pound of target body weight; protein improves satiety and supports muscle preservation during weight loss. Include healthy fats from fish, nuts, olive oil, and avocados; fat slows gastric emptying and prolongs satiety.

Calorie reduction is necessary for weight loss. Most people lose weight with a deficit of 500 calories daily (producing 1 lb weekly weight loss). A combination of reduced food intake and increased activity produces this deficit. Metformin may facilitate modest calorie reduction by improving blood sugar stability and reducing cravings, but willful dietary change is essential. Using a food tracking app or keeping a food diary reveals eating patterns and calorie intake, which helps identify where calories can be reduced.

Regular physical activity accelerates weight loss and improves the metabolic benefits of metformin. Aim for 150 minutes of moderate-intensity aerobic exercise weekly (brisk walking, jogging, cycling) and 2-3 sessions of resistance training weekly. Resistance training is particularly important because it preserves muscle mass during weight loss; metformin supports muscle preservation better than GLP-1 agonists, making combined metformin plus resistance training very effective.

Sleep and stress management significantly influence weight loss success. Poor sleep (less than 7 hours nightly) and high stress increase cortisol levels, promote insulin resistance, and increase cravings. Prioritize 7-9 hours of sleep nightly and implement stress reduction practices like meditation, yoga, or simple breathing exercises. These lifestyle factors often produce as much impact on weight loss as the medication itself.

Long-Term Management and Weight Maintenance

Achieving weight loss is the first phase; maintaining that loss long-term is often more challenging. Understanding strategies for long-term success increases the likelihood of sustained results from metformin therapy.

Most patients taking metformin can maintain weight loss indefinitely if lifestyle changes become permanent habits. The key is ensuring that the dietary changes, exercise routines, and behavioral modifications implemented during active weight loss become sustainable long-term. Many people regain weight after stopping metformin because they return to previous eating and activity patterns. Conversely, those who maintain the lifestyle changes keep the weight off even if metformin is discontinued.

For some patients, metformin represents long-term therapy for life, especially those with prediabetes or type 2 diabetes. The medication prevents or delays diabetes development while supporting modest weight maintenance. For others, metformin may be used for 6-12 months to achieve weight loss goals, then discontinued once eating and activity habits are established.

Annual monitoring is recommended for long-term metformin users. This includes kidney function testing (creatinine, eGFR), liver function tests, vitamin B12 levels, and assessment of blood glucose and HbA1c (if prediabetic or diabetic). This monitoring ensures the medication remains safe and effective and detects any developing complications early.

If weight regain occurs despite lifestyle maintenance, options include: dose increase if below 2,000 mg daily (modest additional benefit possible), adding another medication (like GLP-1 agonist if insurance and cost allow), or renewed focus on diet and exercise. Some patients cycle metformin use, taking it for 12 months for weight loss, stopping it for 6 months, then resuming if weight gain occurs. While unconventional, this approach is safe and may work for some individuals.

Metformin for Weight Loss in Special Populations

Certain populations warrant special consideration when using metformin for weight loss. Older adults, women of reproductive age, and those with medical comorbidities may require dose adjustments or additional monitoring.

Older adults (age 65+) have reduced kidney function compared to younger people, increasing metformin accumulation risk. Kidney function should be assessed before starting metformin and annually during treatment. Doses above 1,500 mg daily may be inappropriate in older adults with reduced kidney function. However, properly dosed metformin is safe and often beneficial in healthy older adults, reducing diabetes risk and supporting modest weight loss.

Women planning pregnancy should discuss metformin with their provider before starting. While metformin appears safe in pregnancy and doesn\'t increase birth defects, the evidence is less extensive than for other medications. Women with PCOS who are trying to conceive should continue metformin because it improves ovulation and fertility. For non-pregnant women, metformin can be safely continued throughout pregnancy if needed for diabetes or PCOS management.

Patients with kidney disease require dose reduction. Metformin is generally contraindicated in patients with eGFR < 30 mL/min. In patients with eGFR 30-45, maximum doses should not exceed 1,000 mg daily. As kidney function naturally declines with age, older patients warrant more frequent monitoring and potential dose reductions.

Patients with liver disease or active alcohol abuse should avoid metformin due to lactic acidosis risk. Moderate alcohol use is generally safe, but heavy drinkers should avoid metformin or be aware of increased risks.