Diabetes: Switching to Sulfonylureas from Metformin Linked to Increased Side Effects

MedicalResearch.com Interview with:

Samy Suissa, PhD Director, Centre for Clinical Epidemiology, Lady Davis Institute Professor, Departments of Epidemiology and Biostatistics and of Medicine McGill University

Dr. Suissa

Samy Suissa, PhD
Director, Centre for Clinical Epidemiology, Lady Davis Institute
Professor, Departments of Epidemiology and Biostatistics and of Medicine
McGill University 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Sulfonylureas are widely used oral antidiabetic drugs that are recommended as second-line treatments after first-line metformin to treat patients with type 2 diabetes. While their safety has been studied extensively, studies in patients with poorly controlled diabetes in need of pharmacotherapy escalation have been sparse and limited. Our study evaluated whether adding or switching to sulfonylureas after initiating metformin treatment is associated with increased cardiovascular or hypoglycaemic risks, compared with remaining on metformin monotherapy.

Using a large cohort of over 77,000 patients initiating treatment with metformin monotherapy, we found that adding or switching to sulfonylureas is associated with modest increases of 26% in the risk of myocardial infarction and 28% in the risk of death, as well as an over 7-fold major increase in the risk of severe hypoglycaemia leading to hospitalisation.

In particular, we found that switching from metformin to sulfonylureas was associated with higher risks of myocardial infarction and death, compared with adding sulfonylureas to metformin.  Continue reading

Metformin Reverses Some Autism Symptoms In Animal Model

MedicalResearch.com Interview with:
Ilse Gantois, PhD

Research Associate
Dr. Nahum Sonenberg’s laboratory
Department of Biochemistry
McGill University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by cognitive impairment and affects 1 in 4000 males and 1 in 6000 females. About 60% of persons with Fragile X also have autism spectrum disorder. FXS is caused by absence of Fragile X protein (FMRP), which results in hyperactivation of ERK (extracellular signal-regulated kinase) and mTORC1 (mechanistic target of rapamycin complex 1) signaling. We show that treatment with metformin, the most widely used FDA-approved antidiabetic drug, suppresses translation by inhibiting the ERK pathway, and alleviates a variety of behavioural deficits, including impaired social interaction and excessive grooming. In addition, metformin also reversed defects in dendritic spine morphogenesis and synaptic transmission.
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Syrosingopine Plus Metformin Have Potential Anti-Cancer Effects

MedicalResearch.com Interview with:
Dr. Don Gary Benjamin
Biozentrum, University of Basel
Basel, Switzerland.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We initiated the study to find a co-drug that would increase the anti-cancer effect of the commonly prescribed anti-diabetic drug metformin. Metformin is a very well tolerated medication, however the dosage required to show anti-cancer activity is higher than that usually prescribed, hence the aim of the study. We found that metformin in combination with a second drug, syrosingopine (an anti-hypertensive), potently kills cancer cells in a variety of pre-clinical models. Quite nicely, both these drugs combine to kill the cells at a concentration where they have no impact on cell growth when applied singly.

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Metformin May Be Underutilized In Patients With Modest Kidney Disease

MedicalResearch.com Interview with:
James Flory MD, MSCE
Division of Endocrinology and Department of Healthcare Policy and Research
Weill Cornell Medical College, NY NY

Medical Research: What is the background for this study? What are the main findings?

Dr. Flory: Metformin is the first-line drug for type 2 diabetes, with much better evidence for safety and improved clinical outcomes than any alternative. The one major safety concern about metformin is the fear that it can cause lactic acidosis, which led to a Food and Drug Administration black box warning against using metformin in patients with even a modest degree of renal impairment. These fears and warnings were based on serious problems with an older drug in the same class, not on experiences with metformin itself, and over the past 20 years it has become clear that the risk of lactic acidosis with metformin is extremely low, and that this warning against the use of the drug in mild renal failure is overly strict. (Dr. Lipska and colleagues published a superb review of this issue a few years back: Diabetes Care June 2011 vol. 34 no. 6 1431-1437)

This is important from a public health perspective because so many patients with diabetes have mild to moderate kidney disease, and we were concerned that the FDA warning was preventing the use of metformin in these patients. Our study was intended to estimate how many patients who would benefit from metformin are not taking it because they have mild kidney disease.

We found that rates of metformin use are much lower in patients with mild kidney disease – just the population where the FDA warning discourages use, but modern data show that metformin is safe. In all, at least 1 million patients with type 2 diabetes who would benefit from metformin appear not to be taking it because clinicians are following the FDA warning and being too conservative.
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Metformin May Extend Lifespan By Increasing Reactive Oxygen Species

Wouter De Haes Functional Genomics and Proteomics (Schoofs lab) Zoological Institute Leuven BelgiumMedicalResearch.com Interview with:
Wouter De Haes
Functional Genomics and Proteomics (Schoofs lab)
Zoological Institute
Leuven Belgium


MedicalResearch: What are the main findings of the study?

Answer: We discovered that the lifespan-extending effect of metformin is dependent on the increased production of reactive oxygen species in the roundworm Caenorhabditis elegans. Antioxidants, compounds that remove these reactive oxygen species, abolished the lifespan-extending effect of metformin, adding to the growing body of evidence that anti-oxidants are not as beneficial for health as generally assumed. We also identified the protein, belonging to the group of peroxiredoxins, that seems responsible for translating this increase in reactive oxygen species production into longevity.
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Diabetes: Study Finds Once Weekly Dulaglutide Lowers HbA1c

MedicalResearch Interview with:
Dr. Valeria Pechtner
Medical Advisor,
Lilly Diabetes

MedicalResearch: What are the main findings of the study?

Dr. Pechtner: Used as monotherapy, once-weekly dulaglutide resulted in significant, sustained glycemic lowering, as measured by HbA1c change from baseline. Both the 1.5 mg and the 0.75 mg dose were superior to metformin at the primary endpoint of 26 weeks. At 52 weeks, dulaglutide 1.5 mg continued to demonstrate superiority to metformin, with dulaglutide 0.75 mg showing non-inferiority. In addition, a majority of patients in all arms achieved the American Diabetes Association’s recommended HbA1c target of less than 7 percent, with more patients achieving this goal in the dulaglutide groups at the 26-week endpoint, and more patients achieving the target in the dulaglutide 1.5 mg group at the 52 week timepoint.

Additionally, dulaglutide 1.5 mg and metformin resulted in similar weight loss. The tolerability and safety profile was comparable for both medications.
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PCOS: Metformin and Weight Loss

Dr. Dorte Glintborg PhD Senior Hospital Physician, PhD Dorte Glintborg, Department of Endocrinology, OUH Odense University HospitalMedicalResearch.com Interview with:
Dr. Dorte Glintborg PhD
Senior Hospital Physician, PhD Dorte Glintborg, Department of Endocrinology, OUH Odense University Hospital

MedicalResearch.com: What are the main findings of this study?

Dr. Glintborg: The main finding of the study is that one year’s metformin treatment is associated with a minor but significant weight loss in patients with PCOS irrespective of BMI at study inclusion. Treatment with oral contraceptives improves sex-hormone levels but is associated with at minor weight gain. Based on the study results, clinicians should consider the combined treatment with metformin and oral contraceptives in patients with PCOS.

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