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Abstracts of Interest at the 78th ADA Scientific Sessions

Jul 14, 2018

ADA 2018 abstracts of interest include Entresto for the Treatment of Diabetic Peripheral Neuropathy; Oral Contraceptive Associated with Postmenopausal Diabetes; Glucokinase as Adjunct Therapy in People with Type 1 Diabetes, and more.


ADA: Entresto for the Treatment of Diabetic Peripheral Neuropathy

Past studies were done on the combination drug of a neprilysin inhibitor with an angiotensin II receptor blocker. It is hypothesized that sacubitril/valsartan (Entresto) is not only effective in heart failure, but also diabetic peripheral neuropathy. Entresto was compared to valsartan alone in rats with type 2 diabetes. They were treated daily with valsartan or sacubitril/valsartan with early intervention (4 weeks post-hyperglycemia) and late intervention (12 weeks post-hyperglycemia). Extensive evaluation after treatment was done to evaluate the effects on vascular and neural complications caused by diabetic neuropathy. Results showed that vascular and neural function had greater improvement with sacubitril/valsartan than with valsartan alone. In the late intervention group, vascular and neural complications were well established before treatment began. Sacubitril/valsartan not only slowed the progression of the deficits, but also stimulated regeneration of the vascular activity and sensory nerves of the skin and cornea, and increased velocity and conduction of nerves. As this drug is already FDA approved for the treatment of heart failure, clinical trials may progress quickly for its use in diabetic neuropathy.

Number: 59-OR | Type: Oral Presentations – ADA 78th Scientific Sessions

Session Title: What’s New in Diabetic Neuropathy? Equal Parts Clinical and Basic Science

Amanda Cortes, PharmD Candidate, LECOM School of Pharmacy

ADA: Luseogliflozin Prevents the Progression of Diabetic Nephropathy

SGLT2 inhibitors have demonstrated to be renoprotective in diabetic nephropathy, but their preventive mechanisms are not yet clear. Luseogliflozin, an SGLT2 inhibitor, has been studied to assess its effects on hypoxia-induced tubular interstitial fibrosis in which hypoxia-inducible factor 1 alpha (HIF-1a) plays a major role. Luseogliflozin was found to decrease the expression of HIF-1a in both cultured human renal proximal tubule epithelial cells and in the kidneys of mice with diabetes. It also inhibited mRNA expression for the genes that encode for HIF-1a. Luseogliflozin was administered to people with diabetes and mice with diabetes for 8 weeks at a dose of 15 mg/kg/day. Luseogliflozin not only lowered blood glucose but also decreased the length of mitochondria in the renal proximal tubules, decreased the thickening of the glomerular basement membrane, and decreased the accumulation of fibronectin in people and mice with diabetes. By suppressing mitochondria respiration, HIF-1a expression is reduced and the people with diabetes can be protected from hypoxia induced renal fibrosis.

Reference: Luseogliflozin Inhibits HIF1α Expression in Renal Proximal Tubular Epithelial Cells; Number: 90-OR | Type: Oral Presentations- ADA 78th Scientific Sessions 2018 – Session Title: What Is New in Diabetic Kidney Disease? (With State-of-the-Art Lecture and ADA Presidents’ Select Abstract)  

Amanda Cortes, PharmD Candidate, LECOM School of Pharmacy

ADA: Dapagliflozin Plus Saxagliptin vs. Add-on Insulin Glargine

Many patients’ diabetes is inadequately managed with metformin alone. Sulfonylureas and basal insulins are typically the drugs of choice when an additional medication is needed as an add-on. However, these drugs are known to cause hypoglycemia and weight gain. Patients who need insulin are also associated with poorer qualities of life. In an international randomized trial, the effects on A1c and quality of life were compared between patients treated with metformin, saxaglitin, and dapagliflozin (N=324) compared to metformin plus basal insulin glargine (n=319). A1c’s were measured and pro-questionnaires were obtained at baseline, at 12 weeks and at 24 weeks. Despite comparable A1c measurements, overall satisfaction, weight gain concern, pain, and regimen acceptance were seen in the dapagliflozin plus saxagliptin group compared to the insulin group. These results suggest that A1c can be managed  just as effectively with the addition of an SGLT2 inhibitor and a DPP-4 inhibitor to metformin and ultimately leads to a better quality of life in most patients compared to add-on insulin.

Dapagliflozin plus Saxagliptin Shows Noninferior A1C Reduction vs. Insulin Glargine in Patients with Type 2 Diabetes Inadequately Controlled by Metformin With or Without Sulfonylurea [Presentations]

Reference: Number: 260-OR | Type: Oral Presentations – Session Title: SGLT2 Inhibitors—From Mechanisms to Clinical Trials (With ADA Presidents’ Select Abstract) –

Amanda Cortes, PharmD Candidate, LECOM School of Pharmacy

ADA: Glucokinase as Adjunct Therapy in People with Type 1 Diabetes

TTP399 is an oral liver selective glucokinase activator that is currently being studied for use as adjunct therapy in type 1 diabetes. It was first tested in patients with type 2 and showed increased times of glucose in target ranges, reduction in post-prandial glucose, and decreased hypoglycemia and hyperglycemia. The Simplici-T1 trial is a 3-phase trial (sentinel, learning phase, and confirming phase) conducted to assess the effects of TTP399 in people with type 1 diabetes. The objectives of the trial are to determine the safety of TTP399, its effect on A1c, and whether TTP399 can replace or reduce bolus insulin doses at mealtime. In the sentinel phase of the study, five patients with type 1 who were on insulin pumps were treated with TTP399. Results showed that TTP399 was well-tolerated and bolus doses were able to be reduced while maintaining glucose within the target range without incidences of hypoglycemia or diabetic ketoacidosis. The study then was able to continue to the randomized, placebo-controlled phase of the study.

Simplici-T1—First Clinical Trial to Test Activation of Glucokinase as an Adjunctive Treatment for Type 1 Diabetes[Presentations] – Number: 126-LB | Type:

Late Breaking Poster Session; Session Title: Late Breaking Poster Session – ADA 78th Scientific Sessions 2018

Amanda Cortes, PharmD Candidate, LECOM School of Pharmacy

ADA: Oral Contraceptive Associated with Postmenopausal Diabetes

In a cross-sectional study, data was collected from the Korea National Health and Nutrition Examination Survey. Postmenopausal women were included in the investigational analysis of the long-term use of oral contraceptives and their effects on the development of diabetes and insulin resistance. Results showed that the incidence of diabetes was higher in those women who had taken oral contraceptives for six months or more compared to women who had never taken oral contraceptives. Longer durations of oral contraceptive use was directly proportional to the prevalence of diabetes and increased insulin resistance in participants without diabetes. Fasting glucose and insulin levels were shown to be higher in participants who took OCs for months or longer. To conclude, these results suggest that prolonged use of oral contraceptives during child-bearing years is a positive risk factor for the development of diabetes in postmenopausal women.

Use of Oral Contraceptives at Child-Bearing Age Are Associated with the Prevalence of Diabetes in Postmenopausal Women [Presentations] – Number: 177-OR | Type: Oral Presentations – Session Title: Diabetes Complications and Risk Factors –  ADA 78th Scientific Sessions 2018

Amanda Cortes, PharmD Candidate, LECOM School of Pharmacy

ADA: Metformin in Cardiovascular Protection in Youth with Type 1 Diabetes

Cardiovascular disease is the leading cause of death in patients with type 1 diabetes due to insulin resistance. It was hypothesized that metformin decreases insulin resistance and vascular health in youth with type 1 diabetes. In the EMERALD study, patients were randomized 1:1 and given 2 grams of metformin or placebo daily. Cardiovascular function was evaluated with MRI’s of the ascending or descending aorta to determine aortic pulse wave velocity and wall shear stress. Insulin resistance was measured using DXA scans, ultra-sound of the carotid intima-media thickness, and fasting labs of overnight IV glycemic control. After three months, the metformin group had decreased insulin resistance and improved aortic and carotid health. These results suggest that metformin may be beneficial as a cardiovascular protective intervention.

SGLT2 Inhibitors—From Mechanisms to Clinical Trials (With ADA Presidents’ Select Abstract) [Sessions] Type: Oral Presentations; Monday, June 25, 2018 at 8:00 AM – 10:00 AM | Location: W415B (Valencia Ballroom)  ADA 78th Scientific Sessions 2018 –

Amanda Cortes, PharmD Candidate, LECOM School of Pharmacy