Metformin for Obesity

Overseen By Gail Thames, BA

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, Los Angeles

Must not be taking: Insulin, Metformin, SU, SGLT2i

Disqualifiers: T2D, Renal impairment, Liver problems, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether the diabetes drug Metformin can aid weight loss when combined with a low-calorie diet. It aims to assess how Metformin affects quality of life and physical activity in individuals who are obese or overweight with a large waist. Researchers will divide participants into two groups: one taking Metformin and the other a placebo, both with dietary changes. The trial seeks adults with a BMI of 27 or higher and a waist over 40 inches for men or 35 inches for women. As a Phase 4 trial, Metformin is already FDA-approved and proven effective, and this research seeks to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot participate if you are currently using insulin or certain diabetes medications like metformin, SU, SGLT2i, glitazone, DPP4, or GLP-1 agonist injections.

What is the safety track record for Metformin?

Research has shown that Metformin is generally safe for use. Studies have found it to be well-tolerated, even with long-term use. For instance, one study involving obese participants demonstrated that Metformin aided in weight loss. After one year, 29% of participants lost at least 5% of their starting weight. Common side effects include fatigue and low vitamin B12 levels. However, serious issues like very low blood sugar and lactic acidosis (a rare but serious acid build-up in the blood) are uncommon. Overall, Metformin is considered a safe and effective medication, particularly for those with type 2 diabetes. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for obesity, which often include lifestyle changes, medications like orlistat, and even bariatric surgery, metformin is being explored for its potential to aid weight loss. Metformin is traditionally used to manage blood sugar in type 2 diabetes but is now being tested for its impact on weight management due to its unique mechanism of action, which can improve metabolic health and reduce appetite. Researchers are excited because metformin might offer an effective and less invasive option compared to surgery, with fewer side effects than other weight loss drugs. Plus, its extended-release form could enhance patient adherence by minimizing the need for frequent dosing.

What is the effectiveness track record for Metformin in treating obesity?

Research has shown that metformin, which participants in this trial may receive, can aid in weight loss. One study found that people taking metformin lost an average of 5.8 kg, while those not taking it gained weight. Another study reported that individuals using metformin lost about 3.8 kg, whereas those not using it didn't lose much weight. Metformin also helps control blood sugar, benefiting people with obesity. Overall, metformin has demonstrated modest weight loss benefits when combined with lifestyle changes like diet and exercise. This trial will compare the effects of metformin extended release (ER) with a placebo, both in combination with a hypocaloric diet. ^{6 7 8 9 10}

Who Is on the Research Team?

Vijiya Surampudi, MD

Principal Investigator

University of California, Los Angeles

Are You a Good Fit for This Trial?

Adults over 18 with obesity, specifically those with a waist size over 40 inches for men and over 35 inches for women, and a BMI of at least 27. Participants must not have had recent severe health events like heart attacks or strokes, any unstable conditions, allergies to metformin, poorly controlled diabetes (HbA1c >7.5), significant kidney issues (eGFR <45 mL/min/1.73 m2), thyroid disease without stable treatment for the past six months, weight changes greater than 11 pounds in the last three months, certain diabetes medications use including insulin or oral metformin, history of lactic acidosis or liver problems.

Inclusion Criteria

Waist circumference >40" for men, and >35" for women

Body Mass Index (BMI) ≥ 27 kg/m2

Exclusion Criteria

I have liver issues.

I have had surgery recently.

History or lactic acidosis

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants receive Metformin ER or placebo with a hypocaloric diet for 24 weeks

24 weeks

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Metformin

Trial Overview The trial is testing Metformin Extended Release tablets against placebo pills to see if they help reduce waist circumference when combined with a low-calorie diet in overweight adults. It also examines how Metformin affects quality of life and physical activity levels compared to the placebo.

How Is the Trial Designed?

Group I: Metformin Extended Release (ER) Oral Tablets Experimental Treatment 1 Intervention

This is a 24-week, randomized, double-blinded, two arm parallel clinical trial comparing metformin ER vs. placebo in combination with a hypocaloric diet (-500 kcal/day). 150 individuals with obesity and increased waist circumference will be randomized to taking metformin ER with hypocaloric diet or placebo with hypocaloric diet. All patients will receive dietary and exercise counseling with the intent of reducing their average caloric intake by 500 kcal/day.

Group II: Placebo Placebo Group 1 Intervention

Patients in the placebo arm will be randomized to placebo with hypocaloric diet. All patients will receive dietary and exercise counseling with the intent of reducing their average caloric intake by 500 kcal/day.

Metformin is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Glucophage for:

• Type 2 diabetes

Approved in United States as Glucophage for:

• Type 2 diabetes

Approved in Canada as Glucophage for:

• Type 2 diabetes

Approved in Japan as Glucophage for:

• Type 2 diabetes

Approved in China as Glucophage for:

• Type 2 diabetes

Approved in Switzerland as Glucophage for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

Published Research Related to This Trial

Metformin extended release (ER) provides effective glycaemic control with once-daily dosing, showing similar effectiveness to twice-daily dosing of immediate-release formulations over a 24-week period in clinical trials.

The metformin ER formulation was well tolerated at doses of 1500 and 2000 mg/day, with no increase in adverse events, indicating its safety for patients managing their blood sugar levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin extended release for the treatment of type 2 diabetes mellitus. Schwartz, SL., Wu, JF., Berner, B.[2019]

The review highlights that while there are many innovative drugs being developed for type 2 diabetes, several have faced serious safety issues, leading to their withdrawal or halting of development.

It discusses the current state of treatments, including glitazones, incretin mimetics, SGLT-2 inhibitors, and new experimental drugs, emphasizing the need for better methods to predict and differentiate drug-related adverse events from natural disease occurrences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Benefits and risks of current pharmacotherapy in the treatment of type 2 diabetes]. Schindler, C., Barthel, A., Fischer, S., et al.[2021]

Newly approved antiobesity drugs like lorcaserin and the phentermine/topiramate combination have shown significant weight loss and improvements in cardiometabolic health risks.

While adverse events from these medications are rare and often decrease over time, specific safety concerns must be addressed, highlighting the need for well-trained healthcare providers in obesity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of new antiobesity drugs. Hainer, V.[2018]

Obesity medications are categorized into four groups: antidepressants, stimulants, fat blockers, and diabetes medications, each with unique effects and side effects, but only lorcaserin and orlistat are approved for long-term use.

High costs and the classification of many obesity medications as controlled substances limit access for underserved populations, and there are currently no approved options for pregnant or lactating women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Past, Present, and Future of Pharmacologic Therapy in Obesity. Rodríguez, JE., Campbell, KM.[2016]

Aleglitazar significantly reduced HbA1c levels in patients with type 2 diabetes compared to placebo, indicating its efficacy in managing blood sugar levels over 26 weeks in a study involving 591 participants.

The treatment was generally well tolerated, showing beneficial effects on lipid profiles and insulin resistance, although it was associated with a higher incidence of hypoglycemia compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, safety and tolerability of aleglitazar in patients with type 2 diabetes: pooled findings from three randomized phase III trials. Henry, RR., Buse, JB., Wu, H., et al.[2022]

In a study of 150 patients with type 2 diabetes, extended-release metformin showed comparable efficacy to Glucophage (standard metformin) over 12 weeks, with no significant differences in fasting plasma glucose or HbA1c levels between the two treatments.

Both treatments had mild adverse effects, primarily gastrointestinal, with a slightly higher rate in the extended-release metformin group, but no serious adverse events were reported, indicating that both options are safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of extended-release metformin in treatment of type 2 diabetes mellitus]. Zhang, JP., Yang, WY., Hong, TP., et al.[2022]

Weight reduction significantly improves glycemic control and cardiovascular risk factors in obese individuals with type 2 diabetes, highlighting the importance of weight management in treatment.

Anti-obesity medications like sibutramine and orlistat lead to modest weight loss and improvements in co-morbidities, including type 2 diabetes, although the effectiveness of various drugs can vary in their impact on glucose levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diabesity: are weight loss medications effective? Halpern, A., Mancini, MC.[2019]

Metformin is an effective oral medication for treating non-insulin-dependent diabetes mellitus (type II diabetes) and does not cause hypoglycemia, which is a common side effect of other diabetes medications like sulfonylureas.

The drug is considered safe when proper precautions are taken, including monitoring liver and kidney function, and it has gained widespread use internationally, recently receiving FDA approval under the brand name Glucophage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin: a biguanide. Tanja, JJ., Langlass, TM.[2013]

Weight loss is crucial in preventing and managing Type 2 diabetes, and pharmacological treatments should not only promote weight loss but also improve insulin sensitivity.

Metformin is highlighted as the first-line medication for obese diabetic patients because it effectively reduces insulin resistance and improves blood sugar control without causing weight gain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological treatment of the obese diabetic patient. Scheen, AJ., Lefebvre, PJ.[2018]

Glumetz (M-ER) is a newly approved extended-release formulation of metformin that provides effective and sustained glycemic control with once-daily dosing, showing similar bioavailability to immediate-release metformin taken twice daily.

In clinical trials lasting 24 weeks, M-ER demonstrated good efficacy and was well tolerated, with continued glycemic control maintained in an additional 24-week open-label extension study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical development of metformin extended-release tablets for type 2 diabetes: an overview. Schwartz, SL., Gordi, T., Hou, E., et al.[2013]

The combination tablet of sitagliptin and metformin (Janumet) has been approved by the FDA for patients with Type 2 diabetes who need better glycemic control, either when taking these medications separately or together.

Sitagliptin has been demonstrated to be safe and effective at a daily dose of 100 mg, and its combination with metformin is believed to enhance glycemic control through complementary mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Janumet: a combination product suitable for use in patients with Type 2 diabetes. Reynolds, JK., Neumiller, JJ., Campbell, RK.[2019]

In a 12-week study involving 156 patients with type 2 diabetes, adding imeglimin to metformin therapy resulted in a significant reduction in A1C levels by 0.44% compared to placebo, indicating improved blood sugar control.

Imeglimin also positively affected fasting plasma glucose and the proinsulin/insulin ratio, while demonstrating a safety profile similar to that of metformin alone, suggesting it is a well-tolerated option for enhancing diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of imeglimin as add-on therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy. Fouqueray, P., Pirags, V., Inzucchi, SE., et al.[2021]

Citations

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Metformin: Mechanisms in Human Obesity and Weight Loss The Metformin Study Group showed a statistically significant decrease in 3.8 kg in the metformin group compared to no significant change in the sulfonylurea ...

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Should I consider metformin therapy for weight loss in ... The mean weight loss in the metformin group was 5.8 kg (± 7.0), whereas controls gained 0.8 kg (± 3.5 kg) on average (P < 0.0001).

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Optimizing metformin therapy in practice: Tailoring therapy in ... 5 PATIENTS WITH OBESITY​​ Metformin has shown efficacy in improving glycaemic control, independent of baseline body weight,82 and it has provided ...

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Efficacy and Safety of Metformin for Obesity: A Systematic ... There is some evidence that metformin therapy plus lifestyle interventions has a modest favorable effect on BMI z score and insulin resistance ...

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Metformin (oral route) - Side effects & dosage Metformin does not help patients who have insulin-dependent or type 1 diabetes because they cannot produce insulin from their pancreas gland.

7. packageinserts.bms.com packageinserts.bms.com/pi/pi_glucophage_xr.pdf

GLUCOPHAGE® XR (metformin hydrochloride) Extended- ... In a double-blind, placebo-controlled, multicenter US clinical trial involving obese patients with type 2 diabetes whose hyperglycemia was not adequately ...

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Long-Term Safety, Tolerability, and Weight Loss Associated ... At year 1, 29% in the metformin group had lost ≥5% of their initial body weight, compared with 13% of the placebo group, and at 2 years, 26% of the metformin ...

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7 Metformin Side Effects and the Risks of Long Term Use It can also cause fatigue, weight loss, and low vitamin B12 levels. While uncommon, metformin can also cause blood glucose to drop too low and lactic acidosis.

10. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK518983/

Metformin - StatPearls - NCBI Bookshelf - NIH Metformin is the drug of choice for patients with type-2 diabetes. Metformin is considered a safe and inexpensive medication that offers ...