Author Interviews, Diabetes, Orthopedics / 08.08.2016
New Anti-Diabetic Compound May Avoid Bone Loss Seen With Current Medications
MedicalResearch.com Interview with:
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Dr. Patrick Griffin[/caption]
Patrick Griffin, PhD
Professor
Department of Molecular Therapeutics
The Scripps Research Institute Florida Campus
MedicalResearch.com: What is the background for this study?
Response: Over the past decade, our laboratory and that of TSRI Associate Professor Theodore Kamenecka, have focused on molecules that increase sensitivity to insulin. Using newly discovered information, we have made significant advances in developing a family of drug candidates that target a receptor known as peroxisome proliferator-activated receptors gamma (PPARγ), a key regulator of stem cells controlling bone formation and bone resorption and a master regulator of fat.
Dr. Patrick Griffin[/caption]
Patrick Griffin, PhD
Professor
Department of Molecular Therapeutics
The Scripps Research Institute Florida Campus
MedicalResearch.com: What is the background for this study?
Response: Over the past decade, our laboratory and that of TSRI Associate Professor Theodore Kamenecka, have focused on molecules that increase sensitivity to insulin. Using newly discovered information, we have made significant advances in developing a family of drug candidates that target a receptor known as peroxisome proliferator-activated receptors gamma (PPARγ), a key regulator of stem cells controlling bone formation and bone resorption and a master regulator of fat.
Dr. Lu Qi[/caption]
Lu Qi, MD, PhD, FAHA
HCA Regents Distinguished Chair and Professor
Director, Tulane University Obesity Research Center
Department of Epidemiology
Tulane University
School of Public Health and Tropical Medicine
New Orleans, LA 70112
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Prenatal malnutrition and other stresses may cause small newborn babies, who are more likely develop type 2 diabetes and other chronic diseases during adulthood. However, whether such relation is causal remains to be determined. Genetic associations provide a new approach to provide evidence for such causality.
Dr. Kenneth Cusi[/caption]
Kenneth Cusi, M.D., F.A.C.P., F.A.C.E.
Professor of Medicine
VAMC staff
Chief, Division of Endocrinology, Diabetes and Metabolism
The University of Florida
Gainesville, FL 32610-0226
MedicalResearch.com: What is the background for this study?
Dr. Cusi: Many patients with prediabetes or Type 2 Diabetes Mellitus (T2DM) are not diagnosed with Nonalcoholic steatohepatitis (NASH), a disease that is the second cause of liver transplantation in the United States. It is also associated with worse cardiovascular disease and harder to control T2DM. We had done in this population a proof-of-concept study published in Nov 2006 in the NEJM. But we lacked a larger, long-term study for definitive proof. This is the largest SINGLE center study, and the longest ever (3 years).
NASH is an overlooked problem for perhaps as many as one-third of patients with Type 2 Diabetes Mellitus. There is now a safe and effective treatment option for patients with T2DM and NASH – pioglitazone will become for NASH what metformin is to the treatment of T2DM: a safe, effective, the “backbone therapy" to which other treatments will be added.
Dr. Andrea M. Kriska PhD MS
Professor, Department of Epidemiology
Graduate School of Public Health
Pittsburgh, PA 15261
MedicalResearch.com: What is the background for this study?
Dr. Kriska: The Diabetes Prevention Program (DPP) was a well administered national research study primarily supported by the National Institutes of Health (NIDDK) that demonstrated that lifestyle intervention with weight loss and physical activity goals can prevent type 2 diabetes in diverse, high risk US adults. The importance of physical activity in preventing diabetes development in the DPP until now was thought to be due to its role in achieving weight loss and weight maintenance but activity was not considered a strong key factor alone.
The lifestyle group had a significantly greater increase in physical activity and decrease in weight than the other two groups. They also had a 58% decrease in diabetes incidence compared to the control group. The successful decrease in T2D held across all age, sex, baseline BMI and ethnicity/race subgroups.
Despite the fact that the lifestyle intervention was then offered to all participants, in the follow-up years, the lifestyle participants still maintained a lower cumulative diabetes incidence that could not be explained by differences in weight loss.
Prof. David Halon[/caption]
Prof. David A. Halon MB ChB, FACC, FESC
Associate Professor of Clinical Medicine
Technion, Israel Institute of Technology.
Director, Interventional Cardiology
Lady Davis Carmel Medical Center
Haifa, Israel
MedicalResearch.com: What is the background for this study?
Prof. Halon: Type 2 diabetics are well known to have more cardiovascular events than non-diabetics but even among diabetics this risk is heterogeneous and some remain at very low risk. It remains uncertain if additional diagnostic modalities over and above clinical risk scores may be helpful in defining which diabetics are at high risk for an adverse event. We performed a study using cardiac CT angiography (CCTA) in 630 type 2 diabetics 55-74 years of age with no history of coronary artery disease to examine if CTA findings would have additional prognostic value over traditional risk scores for cardiovascular or microvascular based events over 7.5 years of follow-up.
Prof. Philip Home[/caption]
Professor Philip Home D.M., D.Phil
Professor of Diabetes Medicine
Newcastle University
MedicalResearch.com: What is the background for this study? What are the main findings?
Prof. Home: MK1293 is a biosimilar insulin designed with the same amino acid sequence, manufacturing process and formulation as originator insulin glargine (Lantus). This is the clinical proving study in type 1 diabetes, being a 24-week randomized study in 508 participants between MK1293 and Lantus. The primary efficacy endpoint of non-inferiority of HbA1c was met, as was a secondary of equivalence (difference in change from baseline 0.04 (95% CI -0.11, 0.19) %-units), with other measures including hypoglycaemia, insulin antibodies and adverse events also consistent with similarity.
Ambika Satija[/caption]
Ambika Satija
Departments of Nutrition & Epidemiology
Harvard T. H. Chan School of Public Health
Boston, MA
MedicalResearch.com: What is the background for this study?
Response: In this study, we followed more than 200,000 male and female health professionals across the U.S. for more than 20 years who had regularly filled out questionnaires on their diet, lifestyle, medical history, and new disease diagnoses as part of three large long-term studies.
Dr. Heerspink[/caption]
Doctor Hiddo Lambers Heerspink
Department of Clinical Pharmacy and Pharmacology
University Medical Center Groningen
the Netherlands
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: SGLT2 inhibitors, including canagliflozin, have beneficial effects on multiple cardiovascular and renal risk parameters. This suggests that SGLT2 inhibitors may confer cardiovascular and renal protection. A recent large clinical trial with the SGLT2 inhibitor empagliflozin demonstrated marked reductions in cardiovascular morbidity and mortality and suggested possible renoprotective effects. Whether SGLT2 inhibition slows the progression of kidney function decline independent of its glucose-lowering effect, however, is unknown. We therefore assessed whether canagliflozin slows the progression of kidney function decline by comparing the effects of canagliflozin versus glimepiride on eGFR and albuminuria.
Dr. Rozalina McCoy[/caption]
Rozalina McCoy, M.D
Assistant Professor of Medicine
Division of Primary Care Internal Medicine
Department of Medicine
Mayo Clinic Rochester
MedicalResearch.com: What is the background for this study?
Dr. McCoy: Hypoglycemia is a serious potential complication of diabetes treatment; it worsens quality of life and has been associated with cardiovascular events, dementia, and even death. Most professional societies recommend targeting HbA1C levels less than 6.5% or 7%, with individualized treatment targets based on patient age, other medical conditions, and risk of hypoglycemia with therapy. Treating patients to very low HbA1c levels is not likely to improve their health, especially not in the short-term, but can cause serious harms such as hypoglycemia. The goal of our study was to assess how frequently patients with type 2 diabetes are treated intensively, focusing specifically on patients who are elderly or have serious chronic conditions such as dementia, kidney disease including dialysis need, heart disease, stroke, lung disease, and cancer. Moreover, while prior studies have suggested that intensive treatment may be common, there was no strong evidence that intensive treatment does in fact increase risk of hypoglycemia. Our study was designed specifically to assess this risk.
We examined medical claims, pharmacy fill data, and laboratory results of 31,542 adults with stable and controlled type 2 diabetes who were included in the OptumLabs™ Data Warehouse between 2001 and 2013. None of the patients were treated with insulin or had prior episodes of severe hypoglycemia, both known risk factors for future hypoglycemic events. None of the patients had obvious indications for very tight glycemic control, such as pregnancy.
“Intensive treatment” was defined as being treated with more glucose-lowering medications than clinical guidelines consider to be necessary given their HbA1C level. Patients whose HbA1C was less than 5.6 percent (diabetes is defined by HbA1C 6.5 percent or higher) were considered intensively treated if they were taking any medications. Patients with HbA1C in the “pre-diabetes” range, 5.7-6.4 percent, were considered to be intensively treated if using two or more medications at the time of the test, or if started on additional medications after the test, because current guidelines consider patients with HbA1C less than 6.5 percent to already be optimally controlled. For patients with HbA1C of 6.5-6.9 percent the sole criteria for intensive treatment was treatment intensification with two or more drugs or insulin.
The patients were separated by whether they were considered clinically complex (based on the definition by the American Geriatrics Society)—75 years of age or older; or having end-stage kidney disease, dementia; or with three or more serious chronic conditions. This distinction has been made to help identify patients for whom adding glucose-lowering medications is more likely to lead to treatment-related adverse events, including hypoglycemia, while not providing substantial long-term benefit.
