Paternal metformin use associated with major birth defects if used during period of sperm development

1. Paternal metformin use associated with major birth defects if used during period of sperm development

Abstract: https://www.acpjournals.org/doi/10.7326/M21-4389    

Editorial: https://www.acpjournals.org/doi/10.7326/M22-0770  

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A large cohort study found that babies born to men who took metformin during the period of sperm development were at increased risk for birth defects, specifically genital defects in boys. These finding suggest that men with diabetes who are taking metformin should talk to their doctors about whether they should switch to another treatment when trying to conceive a child. However, because diabetes control also affects sperm quality, discontinuing metformin treatment could also affect birth outcomes. The findings are published in Annals of Internal Medicine.

Diabetes increasingly occurs in people of reproductive age, compromises sperm quality, and is associated with impaired male fertility. Some diabetes drugs may also affect male reproductive health.

Researchers from the University of Southern Denmark and Stanford University studied data from nation-wide national registries of births, patients, and prescriptions to evaluate whether the risk for birth defects varied among offspring born to men treated with insulin, metformin, or sulfonylureas prior to conception. Babies were considered exposed to a diabetes drug if their father filled at least 1 prescription during the 3 months when the fertilizing sperm were developing. The researchers compared birth defects in the babies across diabetes drugs, different times of taking the drug relative to development of fertilizing sperm, and with unexposed siblings of the babies. Babies whose fathers took insulin had no increased risk for a birth defect compared with the general group. Babies whose fathers took metformin had an increased risk for birth defects. There were too few babies whose fathers took sulfonylureas to determine risks for birth defects with any certainty. Taking metformin before or after sperm development did not increase the risk for birth defects. Unexposed siblings were also not at increased risk. According to the authors, the size of the diabetes pandemic suggests that treatment of prospective fathers with diabetes, including pharmacologic management and counseling on diet, physical exercise, and weight loss, should be subject to further study.

An editorial from Germaine M. Buck Louis, PhD, MS at George Mason University emphasizes the importance of corroborating the findings, given the prevalence of metformin use as first-line therapy for type 2 diabetes. The author also calls for guidance from clinicians to help couples planning pregnancy weigh the risks and benefits of paternal metformin use relative to other medications.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with the corresponding author, Maarten J. Wensink, MD, PhD, please contact email him directly at mwensink@health.sdu.dk. Professor Michael Eisenberg can be reached at  eisenberg@stanford.edu and co-author, Professor Rune can be reached at rjacobsen@health.sdu.dk.

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2. Motivational interviewing does not seem to increase effectiveness of weight loss programs

Abstract: https://www.acpjournals.org/doi/10.7326/M21-3128    

Editorial: https://www.acpjournals.org/doi/10.7326/M22-0715

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A meta-analysis of randomized control trials found that a type of talk therapy called motivational interviewing did not increase the effectiveness of behavioral weight management programs (BWMP) for patients with obesity or who were overweight. The findings suggest that given the intensive training required for its delivery, motivational interviewing may not be a worthwhile addition to BWMP. The analysis is published in Annals of Internal Medicine.

Almost two billion adults and 340 million children and adolescents globally are living with overweight or obesity. Excess weight increases risk for cardiovascular disease and some types of cancer and worsens psychosocial health. BWMP focus on weight loss through changes in diet and physical activity and are considered effective treatments for overweight and obesity and may improve psychological well-being. Motivational interviewing is a psychotherapeutic intervention engages patients in behavior change.

Researchers from the University of Oxford conducted a meta-analysis of 46 studies comprising 11,077 participants to assess the independent contribution of motivational interviewing as part of a BWMP in controlling weight and improving psychological well-being. Studies assessed motivational interviewing to determine if it increased weight loss or enhanced weight maintenance compared with no or minimal intervention; increased weight loss or enhanced weight maintenance when used with weight management interventions compared with a similar weight management intervention without motivational interviewing; and if motivational interviewing improved psychological well-being. The authors found that compared to no or minimal intervention, programs incorporating motivational interviewing led to about 1 kg greater weight loss in adults at 3 and 6 months of follow-up. However, only two studies provided weight data after a year, with no evidence of a sustained difference. The authors also found that no evidence that incorporating motivational interviewing into a BWMP improved weight loss at any time point compared with either similar-intensity or lower-intensity BWMPs. Additionally, the authors found no evidence that incorporating motivational interviewing improved psychological wellbeing.

An editorial from authors at the NYU Grossman School of Medicine asserts that MI has a negligible impact on weight management because obesity is impacted by complex factors outside the patient’s control, including genetics, inflammation, medications, composition of the microbiome, psychological stress, chronic pain, access to recreational facilities, access to healthy food, and exposure to environmental toxins. The authors say that although MI isn’t effective as a standalone weight loss intervention, it improves specific health-promoting behaviors which are important for weight management. However, the authors caution providers who use MI or other counseling techniques to avoid exacerbating obesity stigma.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with the corresponding author, Moscho Michalopoulou, MSc, please email moscho.michalopoulou@phc.ox.ac.uk.

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3. Popular iron infusion formulations pose low risk for anaphylaxis

Among formulations studied, risk for anaphylaxis 3- to 8-fold greater for iron dextran and ferumoxytol than for iron sucrose

Abstract: https://www.acpjournals.org/doi/10.7326/M21-4009    

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A retrospective cohort study found that rates of anaphylaxis among the most commonly used intravenous (IV) iron formulations were very low, but were 3- to 8-fold greater for iron dextran and ferumoxytol than for iron sucrose. By clarifying the risk for this rare but severe adverse reaction, this information can contribute to the choice of IV iron preparations. The findings are published in Annals of Internal Medicine.

Anaphalyaxis is an acute systemic allergic reaction that can occur with any IV iron formulation but seems to be a low risk in current IV iron formulations. However, given the rarity of anaphylactic events, clinical trials and analyses are not enough to find differences in anaphylaxis among formulations. Current formulations include low-molecular-weight iron dextran, ferumoxytol, ferric gluconate, iron sucrose, and ferric carboxymaltose.

Researchers from Rutgers University conducted a retrospective cohort study using Medicare data of more than 167,000 beneficiaries between 2013 and 2018 to compare risks for anaphylaxis among the 5 IV iron formulations. Patients were categorized into five groups according to medication received. The authors found that iron sucrose and ferumoxytol were most commonly prescribed, with 59,755 patients and 40,778 patients included in each respective category. The remaining patients received ferric carboxymaltose (36,399), iron dextran (19,225), and ferric gluconate (11,768). After conducting analyses, the authors found that compared to iron sucrose, iron dextran and ferumoxytol had the highest risk of anaphylaxis. The authors reported that risk for anaphylaxis did not differ significantly with gluconate or ferric carboxymaltose compared with iron sucrose. The authors note that the results of the study should be cautiously interpreted as the overall risk of anaphylaxis in all five IV iron formulations is still very low. According to the authors, factors guiding the choice of iron preparation should include not only the risk for anaphylaxis but also medical history, clinical indication, setting, dose, number and duration of administrations needed, risk for other adverse events, and cost.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with the corresponding author, Chintan V. Dave, PharmD, PhD, please email directly to chintandave19@gmail.com.

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