News Release 

Metformin may help patients maintain weight loss long-term

American College of Physicians

1. Metformin may help patients maintain weight loss long-term



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In the Diabetes Prevention Program (DPP) clinical trial and its long-term follow-up study, among the persons who lost at least 5 percent of their body weight during the first year, long-term maintenance of weight loss was more likely if they had been assigned to treatment with metformin than with placebo or lifestyle intervention. Being older and losing a greater amount of weight in the first year were the most consistent predictors of lasting weight loss. Findings from a cohort study are published in Annals of Internal Medicine.

Weight loss plays a central role in efforts to prevent or delay type 2 diabetes. As such, identifying good predictors of long-term weight loss could lead to improved weight management. The DPP was a randomized controlled trial that compared weight loss and diabetes prevention with metformin, intensive lifestyle intervention (ILS), or placebo among more than 3,000 participants with prediabetes, and its Outcomes Study (DPPOS) observed patients after the masked treatment phase ended. The DPP/DPPOS is the largest and longest-running study of metformin for prevention of diabetes.

After the first year, twice as many participants in the ILS group versus the metformin group lost at least 5 percent of their body weight. However, those who were assigned to the metformin group had greater success at maintaining their weight loss between years 6 and 15, while patients were still being followed. The researchers noted that greater weight loss at one year predicted long-term weight loss across all groups. Early weight loss was also important with regard to diabetes incidence. The researchers found that cumulative diabetes incidence rates over 15 years were lower among those who lost at least 5 percent of their weight in the first year.

According to the study authors, future research should focus on whether metformin could be a useful intervention for weight loss maintenance after initial weight loss with lifestyle interventions, antiobesity drugs or devices, or bariatric surgery.

Media contact: For an embargoed PDF, please contact Lauren Evans at To speak with the lead author, Kishore M. Gadde, MD, please contact him via email at, or Lisa Stanbury at

2. Poor glycemic control raises risk for preterm birth


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Risk for preterm birth was strongly linked to maternal HBA1c around the time of conception. Women with HBA1c levels consistent with recommended target levels also seemed to be at risk for preterm delivery as well as other adverse pregnancy outcomes. Findings from a cohort study are published in Annals of Internal Medicine.

Type 1 diabetes is known to complicate pregnancy, but the relationship between maternal glycemic control and preterm birth is less clear. At least three major organizations now recommend a target HBA1c level of less than 6.5 percent in early pregnancy. However, because these recommendations originate from research regarding congenital malformations and large for gestational age infants, whether such strict glycemic control prevents or reduces excess risk for preterm birth in women with type 1 diabetes is not clear.

Researchers at Karolinska Institutet in Stockholm, Sweden use nationwide Swedish registers to examine adverse pregnancy outcomes in more than 2,400 singleton deliveries according to HBA1c levels in mothers with type 1 diabetes. The researchers also examined neonatal death, large for gestational age, macrosomia, infant birth injury, hypoglycemia, respiratory distress, low Apgar score, and stillbirth. They found that increasing HBA1c levels were associated with progressively increased risks for preterm birth, as well as other adverse pregnancy outcomes. Most of the elevated risk for preterm birth was attributable to medically indicated preterm births, although spontaneous preterm births also increased with higher HbA1C levels.

According to the researchers, these findings are important for developing future guidelines and informing clinicians about the risks associated with poor glycemic control. However, the results do not support the idea that further lowering the recommended HBA1c level during early pregnancy will eliminate the risk for preterm birth.

Media contact: For an embargoed PDF, please contact Lauren Evans at To speak with the lead author, Jonas F. Ludvigsson, MD, PhD, please contact Karolinska Institutet's Press Office at or +46 8 524 860 77.

3. National Institutes of Health Pathways to Prevention Workshop Identifies Gaps in Evidence for Effectiveness and Safety of Long-term Osteoporosis Drug Therapies

Summary of review and position paper


Position Paper:


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About 10 million U.S. adults aged 50 years or older have osteoporosis and that number is expected to increase as the population ages. Several osteoporosis drug treatments reduce fractures in the short-term (up to 3 years), but optimal long-term use is uncertain. A systematic review evaluating the benefits and harms of long-term osteoporosis drug treatment and of discontinuation of treatment, or drug holidays, and an accompanying position paper are published in Annals of Internal Medicine.

Researchers funded by the National Institutes of Health Office of Disease Prevention and the Agency for Healthcare Research and Quality who were based at the Geriatric Research Education & Clinical Center in the Minneapolis VA Health Care System and the University of Minnesota Evidence-based Practice Center reviewed 35 trials and 13 observational studies. They found that for mostly treatment-naïve postmenopausal women, compared with placebo, alendronate for 4 years reduced vertebral and nonvertebral fractures in women with osteoporosis, and zoledronic acid for 6 years reduced these fractures in women with osteopenia or osteoporosis. Controlled, observational studies suggested that long-term bisphosphonate treatment may increase risk for serious but still rare adverse events, such as atypical femoral fracture (AFF) and osteonecrosis of the jaw (ONJ). Risk for AFF appears greater with longer use. In women with osteoporosis, raloxifene for 4 years compared with placebo reduced vertebral fractures, but not nonvertebral fractures, and increased risk for deep venous thrombosis and pulmonary embolism. In women with unknown osteoporosis or osteopenia status, oral hormone therapy for 5 to 7 years reduced clinical fractures and hip fractures compared with placebo, but this was offset by increased risk for cardiovascular disease and cognitive impairment, and estrogen-progestin increased risk for invasive breast cancer. Data were insufficient to draw conclusions about the benefits and harms of long-term use of other FDA-approved osteoporosis drugs, including risedronate, ibandronate, denosumab, teriparatide, and abaloparatide.

Data were less clear for informing clinicians about the balance of fracture benefits to harms with bisphosphonate drug holidays. This was because neither alendronate continuation beyond 5 years nor zoledronic acid beyond 3 years versus discontinuation reduced hip or other nonvertebral fractures and only inconsistently reduced vertebral fractures. Also, scant observational data suggested bisphosphonate continuation may increase risk of AFF compared with discontinuation.

According to the National Institutes of Health Pathways to Prevention Workshop report that focused on research gaps for long-term drug therapies for osteoporotic fracture prevention, the evidence was insufficient to determine if implementing drug holidays in some patients could help to reduce the risk of some serious adverse events. The Workshop committee recommends further research in this area. They also recommend research into newer treatments, and into the patient and clinical barriers that prevent people from getting screened and adhering to osteoporosis drug treatment regimens.

Media contact: For an embargoed PDF, please contact Lauren Evans at To interview the lead author, Howard Fink, MD, MPH, please contact Ralph Heussner at


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Ideas and Opinions


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