Abstracts - Orals, Poster Previews, and Posters
FRI 708-718-Novel Treatment for Diabetes- Focusing on GLP-1 and SGLT2 (posters)
Exhibit/Poster Hall (BCEC)
Poster Board FRI 708
Helmsley Charitable Trust Abstract Awards in Type 1 Diabetes
We have recently demonstrated that the addition of liraglutide to insulin significantly improves the glycemic control in patients with type 1 diabetes (T1D). We have now conducted the first prospectively randomized study investigating whether the addition of dapagliflozin, a SGLT-2 inhibitor which induces glycosuria, to insulin and liraglutide would further improve glycemic control. Thirty T1D patients on insulin and liraglutide therapy for at least last 6 months were randomized (in 2:1 ratio, drug: placebo) to receive either dapagliflozin 10mg or placebo daily for 12 weeks. Dapagliflozin was initiated at 5 mg daily for one week and increased to 10 mg daily thereafter. Twenty six patients completed the study (Placebo=9; Dapagliflozin = 17). All patients had T1D for at least one year, on insulin therapy and had no detectable c-peptide in plasma and were on 1.8 mg of liraglutide for 7±1 months (mean body weight: 82.69±3.43 kg; mean HbA1c: 7.68±0.15%, mean weekly glucose levels: 163±6 mg/dl ,total insulin dose: 52.3±4.8 units, mean age: 54±2 years, mean age at T1D diagnosis: 29±2years, mean BP: 122±2/76±1 mmHg, 8 males, 17 females, 23 Caucasian, 1 African American and 1 Asian) with no difference in these parameters between the two groups. HbA1c fell by 0.6±0.08% in the dapagliflozin group (p<0.01 vs placebo) with no changes in placebo group. The average weekly glucose concentration fell in the dapagliflozin group by 15±6 mg/dl (p<0.05 vs baseline, p=0.07 vs placebo) with no changes in placebo group. There was no additional hypoglycemia (<70 mg/dl; p=0.52 vs placebo). The basal insulin dose fell by 0.72±0.96 from 33.70±4.53 units while it increased by 1.9±0.5 units (P<0.01 vs baseline) in placebo (p<0.05 vs placebo). However, total insulin dose remained unchanged in both groups. The body weight fell by 1.9±0.54kg (p<0.05 vs placebo) in the dapagliflozin group while it remained unchanged in placebo group. The total cholesterol and LDL cholesterol increased by 6 and 8% from 167±8 and 90±7 mg/dl (p<0.01 vs placebo for both) in dapagliflozin group while it decreased by 11 and 17% in the placebo group (p<0.05 for both vs baseline) from 176±11 and 89±8 mg/dl respectively. Two of the drop-out patients in Dapagliflozin group developed DKA (one patient with euglycemic DKA with total insulin dose reduced from 33 to 26 units and the other with hyperglycemic DKA with total insulin dose unchanged at 26 units) within 24 hours of increasing the dose to 10 mg daily. This proof of concept study suggests that the addition of dapagliflozin to insulin and liraglutide in patients with T1D results in a significant improvement in glycemia. However, care has to be exercised in terms of the reduction in the insulin dose and increasing dapagliflozin dose to prevent the occurrence of DKA. Longer and larger randomized clinical trials will need to be conducted to establish the durability of the triple therapy in T1D.
Disclosure: NDK: Speaker, Astra Zeneca, Speaker, Novo Nordisk. AC: Speaker, Astra Zeneca, Speaker, Novo Nordisk. PD: Speaker, Astra Zeneca, Speaker, Novo Nordisk. Nothing to Disclose: AM, HG, MG, JH, AM, MB
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