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Poster Summaries of Interest at the 78th ADA Scientific Sessions

Jul 14, 2018

Key ADA poster summaries include liraglutide in type 1 diabetes, oral semaglutide, bottled water’s association with type 2 diabetes, & SGLT-2 combo LIK066.

ADA: Liraglutide in Type 1 Diabetes

In a 52-week trial, the GLP-1 agonist, liraglutide, was added on to insulin therapy in people with type 1 diabetes. Patients were randomized to receive placebo or 1.8 mg of liraglutide daily for one year. Glucose was monitored with a continuous glucose monitor for four weeks before the trial and after the trial. At the end of treatment, HbA1c dropped from 7.9 + 0.15 to 7.45 + 0.12 in the liraglutide group (p <0.006 vs. placebo). Weekly blood glucose fell by 15 mg + 4mg/dL (p< 0.014 vs. placebo) and fasting weekly blood glucose fell from 165 + 7mg/dL to 153 +9mg/dL (p=0.032). There was significant weight loss seen in the liraglutide group compared to the placebo group with a loss in weight of 2.5 kg + 0.9 kg (p = 0.041 vs. placebo). A drop in SBP and DBP was also seen in the liraglutide group (p = 0.031). With these results, GLP-1 agonists, such as liraglutide, show promising benefits in the treatment of type 1 diabetes.

Reference: Dandona, Paresh, et al. “Liraglutide as an Additional Treatment to Insulin in Patients with Type 1 Diabetes Mellitus—A 52-Week Randomized Double-Blinded Placebo-Controlled Clinical Trial.” Diabetes, vol. 67, no. Supplement 1, 2018, doi:10.2337/db18-3-lb.

ADA: Semaglutide: The First Oral GLP-1 Agonist

GLP-1 agonists are used in the treatment of type 2 diabetes, to increase satiety, slow gastric emptying, help with weight loss, and of course improve glycemic control. Semaglutide is in late stage development for the treatment of type 2 diabetes and will be known as the first oral GLP-1 receptor agonist. It is made in a tablet formulation and comes in 3, 7, or 14 mg. The tablet is taken once daily. Sema was assessed for safety and efficacy in a double-blind placebo-controlled trial in people who had type 2 diabetes that was not controlled by diet and exercise and who are drug naïve. The primary endpoint was to see a reduction in HbA1c after 26 weeks of treatment, and the secondary endpoint was to assess its efficacy without the need of rescue medication. Semaglutide resulted in reductions in HbA1c and body weight. These results were seen at all doses. The most common adverse effect reported with Sema was mild to moderate nausea. This effect was transient. Compared to placebo, semaglutide demonstrated better results in weight loss and reduction of HbA1c.

Reference: Aroda, Vanita R., et al. “Effect and Safety of Oral Semaglutide Monotherapy in Type 2 Diabetes—PIONEER 1 Trial.” Diabetes, vol. 67, no. Supplement 1, 2018, doi:10.2337/db18-2-lb.

ADA: A Dual SGLT Inhibitor in the Treatment of Type 2 Diabetes

LIK066 is a potent inhibitor of both SGLT-1 and SGLT-2. SGLT-1 is found in the gut and SGLT-2 is found in the kidneys. LIK066 was assessed for its effects on glucose control, weight, and incretins such as GLP-1, PYY, GIP, glucagon, and insulin. First, a single dose was given to people with type 2 diabetes in a cross-over study, where patients were given 2.5, 30, and 300 mg as single doses. Results showed that with 30 mg and 300 mg, glucose was reduced and insulin secretions were reduced in 12 patients. Patients given the 300 mg dose experienced complete suppression of glucose and insulin excursions. In a separate phase of the study, 30 patients with type 2 were given 15 mg of LIK066 once daily for 14 days. Results showed that glucose was reduced by about 41 mg/dL and 24-hour urinary excretion of glucose was increased (100g per day by day 14). Incretins such as GLP-1 and PYY were increased (p<0.05) after an oral glucose tolerance test. GIP was reduced by about 50% (p<0.05). In a 12-week randomized, double-blinded, placebo-controlled study, 150 mg of LIK066 was administered to 88 patients who had type 2 and obesity. Results of this test revealed weight loss of about 5.7% percent (p<0.001) compared to placebo. LIK066 was found to be safe and well-tolerated with the most common adverse effects reported to be headache, flatulence, and diarrhea. Due to its effects on metabolic parameters and metabolic hormones, this dual inhibition from LIK066 appears to have great potential in the treatment of type 2 diabetes in patients with obesity.

Reference: Aroda, Vanita R., et al. “Effect and Safety of Oral Semaglutide Monotherapy in Type 2 Diabetes—PIONEER 1 Trial.” Diabetes, vol. 67, no. Supplement 1, 2018, doi:10.2337/db18-2-lb.

ADA: Nicotinimide N-methyltransferase Inhibitors Reduce Adipose Tissue, Hyperglycemia, and Insulin Resistance

Because obesity is a leading cause of type 2 diabetes, drugs are in development to reduce adipose tissue. A new drug class called nicotinamide N-methyltransferase (NNMT) inhibitors is being studied in diet-induced obese mice to assess its efficacy, oral bioavailability, and safety. The desired effects of this therapy is to regulate adipose tissue metabolism, and energy homeostasis. Results showed a reduction in adipose cell size, weight reduction, reduced cholesterol levels, and overall reduction of white adipose tissue mass. With these results, a drug class such as NNMT inhibitors may be used in the future to reduce the risk of type 2 diabetes caused by adiposity.

Reference: Neelakantan, Harshini, and Stan Watowich. “Development of Oral Bioavailable Nicotinamide N-Methyltransferase Inhibitors to Reduce Adiposity, Insulin Resistance, and Hyperglycemia.” Diabetes, vol. 67, no. Supplement 1, 2018, doi:10.2337/db18-115-lb.

ADA: The Association of Bottled Water and Type 2 Diabetes

Low water intake and chemicals in some water sources are found to be associated with hyperglycemia. A cohort study of Puerto Ricans with obesity or excess weight showed the association between drinking water sources and prediabetes and diabetes. In 2014 to 2016, 1,023 participants were asked about their sources of drinking water. The primary sources for drinking water was reported to be 52% bottled, 25% filtered, and 23% tap water. Diabetes was assessed using ADA criteria for post-prandial glucose and fasting glucose. Bottled water consumers had higher prediabetes (OR=1.43; 95% CI: 1.02, 2.01) and diabetes findings compared to tap water (OR=1.93; 95% CI: 1.08, 3.46). Filtered water consumers had incidences of prediabetes and diabetes compared to tap water consumers. Controlling the amount of water consumed, sugar-sweetened beverages, or canned food and drinks did not change the results. The prevalence of diabetes was found to be higher in the residents of the city of San Juan, Puerto Rico. The impact of bottled water in causing prediabetes and diabetes may be due to the endocrine mediators found in the plastic of water bottles. Further studies need to be done in order to confirm this association.

Reference: Joshipura, Kaumudi J., et al. “Cross-Sectional Associations between Drinking Bottled Water and Prediabetes/Diabetes.” Diabetes, vol. 67, no. Supplement 1, 2018, doi:10.2337/db18-197-lb.

ADA: Alirocumab in Patients with Diabetes and ACS

Patients with diabetes and a history of acute coronary syndrome are at a higher risk of experiencing ischemic CV events. People with diabetes have better CV effects with intense lipid lowering than those without diabetes. Alirocumab is human monoclonal antibody to PCSK9. In a trial called ODYSSEY OUTCOMES, 18,924 patients with recent ACS and an LDL of 70 mg/dL or more were randomized to receive either 75 mg of alirocumab or placebo subcutaneously every two weeks. These patients were already on the maximum tolerated doses of atorvastatin and rosuvastatin. The primary endpoint was the time to first CV event such as CHD death, nonfatal MI, ischemic stroke or unstable angina requiring hospitalization. Safety and efficacy were assessed looking at baseline glucometabolic status and new onset diabetes. Results showed a better overall cardiovascular risk reduction and lower LDL levels were seen in patients with diabetes who received alirocumab treatment compared to placebo. Also, no new onsets of diabetes were reported.

Reference: Ray, Kausik K., et al. “Alirocumab and Cardiovascular Outcomes in Patients with Acute Coronary Syndrome (ACS) and Diabetes—Prespecified Analyses of ODYSSEY OUTCOMES.” Diabetes, vol. 67, no. Supplement 1, 2018, doi:10.2337/db18-6-lb.