The purpose of the study was to evaluate the performance and usability of the FreeStyle(®) Libre™ Flash glucose monitoring system (Abbott Diabetes Care, Alameda, CA) for interstitial glucose results ...compared with capillary blood glucose results.
Seventy-two study participants with type 1 or type 2 diabetes were enrolled by four U.S. clinical sites. A sensor was inserted on the back of each upper arm for up to 14 days. Three factory-only calibrated sensor lots were used in the study. Sensor glucose measurements were compared with capillary blood glucose (BG) results (approximately eight per day) obtained using the BG meter built into the reader (BG reference) and with the YSI analyzer (Yellow Springs Instrument, Yellow Springs, OH) reference tests at three clinic visits (32 samples per visit). Sensor readings were masked to the participants.
The accuracy of the results was demonstrated against capillary BG reference values, with 86.7% of sensor results within Consensus Error Grid Zone A. The percentage of readings within Consensus Error Grid Zone A on Days 2, 7, and 14 was 88.4%, 89.2%, and 85.2%, respectively. The overall mean absolute relative difference was 11.4%. The mean lag time between sensor and YSI reference values was 4.5±4.8 min. Sensor accuracy was not affected by factors such as body mass index, age, type of diabetes, clinical site, insulin administration, or hemoglobin A1c.
Interstitial glucose measurements with the FreeStyle Libre system were found to be accurate compared with capillary BG reference values, with accuracy remaining stable over 14 days of wear and unaffected by patient characteristics.
OBJECTIVE: To assess the effects of exenatide on body weight and glucose tolerance in nondiabetic obese subjects with normal or impaired glucose tolerance (IGT) or impaired fasting glucose (IFG). ...RESEARCH DESIGN AND METHODS: Obese subjects (n = 152; age 46 ± 12 years, female 82%, weight 108.6 ± 23.0 kg, BMI 39.6 ± 7.0 kg/m², IGT or IFG 25%) were randomized to receive exenatide (n = 73) or placebo (n = 79), along with lifestyle intervention, for 24 weeks. RESULTS: Exenatide-treated subjects lost 5.1 ± 0.5 kg from baseline versus 1.6 ± 0.5 kg with placebo (exenatide - placebo, P < 0.001). Placebo-subtracted difference in percent weight reduction was -3.3 ± 0.5% (P < 0.001). Both groups reduced their daily calorie intake (exenatide, -449 cal; placebo, -387 cal). IGT or IFG normalized at end point in 77 and 56% of exenatide and placebo subjects, respectively. CONCLUSIONS: Exenatide plus lifestyle modification decreased caloric intake and resulted in weight loss in nondiabetic obesity with improved glucose tolerance in subjects with IGT and IFG.
A prior study (PRECISE II) demonstrated that an implantable continuous glucose monitoring (CGM) system (Eversense
CGM System) provided accurate glucose readings through the 90-day sensor life with a ...favorable safety profile in participants with type 1 or type 2 diabetes (T1D, T2D). This study was performed to further characterize the accuracy of the system.
PRECISION was a prospective multicenter study that evaluated the accuracy and safety of Eversense among adults with T1D or T2D through 90 days (NCT02647905). Accuracy measures included percentage system agreement and mean absolute relative difference (MARD) between Eversense and Yellow Springs Instrument reference measurements from 40 to 400 mg/dL. The primary safety endpoint was incidence of device-related or sensor insertion/removal procedure-related serious adverse events (SAEs) through 90 days. An updated glucose calculation algorithm was also applied to the sensor data from the PRECISE II study to evaluate consistency of accuracy results.
Thirty-five participants received the CGM system. Eighty-five percent of CGM values were within 15/15% of reference and the MARD value against reference was 9.6% (95% confidence interval CI: 8.9-10.4). All sensors were functional through day 90. No device- or procedure-related SAEs occurred. Application of the updated algorithm to PRECISE II sensor data resulted in 87% of readings within 15/15% of reference and an MARD value against reference of 8.5% (95% CI: 8.0%-9.1%).
PRECISION corroborated prior accuracy and safety findings of the Eversense CGM System through the 90-day sensor life. The updated algorithm improved accuracy of measurements in PRECISE II.
Aim
To confirm the efficacy and safety of dasiglucagon when administered via an autoinjector device.
Materials and Methods
In this double‐blind trial, 45 participants with type 1 diabetes were ...randomized 3:1 to receive a single subcutaneous dose of dasiglucagon 0.6 mg or placebo following controlled induction of hypoglycaemia. The primary endpoint was time to plasma glucose recovery, defined as a plasma glucose increase of 20 mg/dL or higher from baseline without rescue intravenous glucose.
Results
Median (95% CI) observed time to recovery was 10.0 (8.0; 12.0) minutes for dasiglucagon and 35.0 (20.0; −) minutes for placebo (P < .001). Plasma glucose recovery was achieved within 15 minutes by 88% of participants receiving dasiglucagon versus none receiving placebo (P < .01). Site of injection (buttock or deltoid) was not shown to have any effect on time to recovery (P = .84). No serious adverse events occurred. As expected for glucagon treatment, nausea and vomiting were common adverse events in dasiglucagon‐treated participants.
Conclusions
Dasiglucagon provided rapid reversal of hypoglycaemia in adults with type 1 diabetes. Dasiglucagon administration was well tolerated. The aqueous formulation of dasiglucagon in a ready‐to‐use autoinjector device that can be carried at room temperature may provide a reliable treatment for severe hypoglycaemia.
Hyperglucagonemia contributes to hyperglycemia in patients with type 1 diabetes (T1D); however, novel therapeutics that block glucagon action could improve glycemic control. This phase 2 study ...evaluated the safety and efficacy of volagidemab, an antagonistic monoclonal glucagon receptor (GCGR) antibody, as an adjunct to insulin therapy in adults with T1D. The primary endpoint was change in daily insulin use at week 12. Secondary endpoints included changes in hemoglobin A1c (HbA1c) at week 13, in average daily blood glucose concentration and time within target range as assessed by continuous blood glucose monitoring (CGM) and seven-point glucose profile at week 12, incidence of hypoglycemic events, the proportion of subjects who achieve HbA1c reduction of ≥0.4%, volagidemab drug concentrations and incidence of anti-drug antibodies. Eligible participants (n = 79) were randomized to receive weekly subcutaneous injections of placebo, 35 mg volagidemab or 70 mg volagidemab. Volagidemab produced a reduction in total daily insulin use at week 12 (35 mg volagidemab: -7.59 units (U) (95% confidence interval (CI) -11.79, -3.39; P = 0.040 versus placebo); 70 mg volagidemab: -6.64 U (95% CI -10.99, -2.29; P = 0.084 versus placebo); placebo: -1.27 U (95% CI -5.4, 2.9)) without meeting the prespecified significance level (P < 0.025). At week 13, the placebo-corrected reduction in HbA1c percentage was -0.53 (95% CI -0.89 to -0.17, nominal P = 0.004) in the 35 mg volagidemab group and -0.49 (95% CI -0.85 to -0.12, nominal P = 0.010) in the 70 mg volagidemab group. No increase in hypoglycemia was observed with volagidemab therapy; however, increases in serum transaminases, low-density lipoprotein (LDL)-cholesterol and blood pressure were observed. Although the primary endpoint did not meet the prespecified significance level, we believe that the observed reduction in HbA1c and tolerable safety profile provide a rationale for further randomized studies to define the long-term efficacy and safety of volagidemab in patients with T1D.
Severe hypoglycemia is a major concern for patients with diabetes on insulin therapy. Rescue requires caregivers to provide effective treatment, including glucagon injections. Dasiglucagon is a ...stable glucagon analog in development to be administered with the HypoPal® auto-injector for treatment of severe hypoglycemia. This phase 3 trial, ZP4207-17145, assessed the clinical efficacy and safety of 0.6 mg dasiglucagon subcutaneous (SC) administered via the HypoPal® auto-injector compared with placebo. In total, 45 eligible patients with T1D were randomized (3:1) to dasiglucagon or placebo and dosed following induced hypoglycemia. The primary endpoint was time to plasma glucose (PG) recovery, defined as first PG increase ≥20 mg/dL after treatment initiation without rescue glucose. Dasiglucagon injection provided a fast and effective increase in PG. The median time (95% CI) to recovery based on sampling time was 10 (8.0, 12.0) min for dasiglucagon and 35 (20.0, -) min for placebo (p<0.0001). The median (95% CI) estimated true time to recovery (interpolated between sampling times) was 9.3 (7.8, 10.3) min for dasiglucagon and 25.8 (19.2, 34.8) min for placebo. Nausea and vomiting are well-known side effects of glucagon and were reported in 61.8% and 29.8% of patients receiving dasiglucagon, respectively. Nausea was reported in 10% of patients receiving placebo. No safety concerns were raised for dasiglucagon.
In conclusion, dasiglucagon 0.6mg SC administered via the HypoPal® auto-injector provided fast and effective recovery from hypoglycemia. The results are consistent with previously reported results from a pivotal phase 3 trial testing dasiglucagon administered via a pre-filled syringe, NCT03378635, where a median time to recovery of 10 min was also observed.
Disclosure
T.S. Bailey: Consultant; Self; Abbott, LifeScan, Inc., Novo Nordisk A/S, Sanofi US. Research Support; Self; Abbott, Ascensia Diabetes Care, Capillary Biomedical, Inc., Dance Biopharm Holdings, Inc., Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Kowa Pharmaceuticals America, Inc., Lexicon Pharmaceuticals, Inc., Medtronic, Medtrum, Novo Nordisk A/S, REMD Biotherapeutics, Sanofi-Aventis, Senseonics, Viacyte, Inc., vTv Therapeutics, Zealand Pharma A/S. Speaker’s Bureau; Self; Medtronic, Sanofi US. J. Willard: None. L.J. Klaff: Research Support; Self; Abbott, Ascensia Diabetes Care, Dexcom, Inc., Lilly Diabetes, Medtronic, Novo Nordisk A/S, REMD Biotherapeutics, Roche Diabetes Care, Sanofi-Aventis, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. L.S. List: Employee; Spouse/Partner; Novo Nordisk A/S. Employee; Self; Zealand Pharma A/S. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S, Zealand Pharma A/S. A.E. Melgaard: Employee; Self; Zealand Pharma A/S. R. Tehranchi: Employee; Self; Zealand Pharma A/S.
The efficacy of dasiglucagon 0.6 mg has been investigated in multiple trials in individuals with T1DM. The primary endpoint was time to plasma glucose (PG) recovery from insulin-induced hypoglycemia, ...defined as first PG increase ≥20 mg/dL after treatment initiation without the need for IV glucose. Different PG sampling schemes were used in phase 2 (5-min intervals) versus phase 3 trials (more frequent sampling). Estimating the true but unmeasured time to recovery for each individual enables for a better comparison between trials when compared to use of observed time only. The true time was calculated using linear interpolation between the 2 time points before and after recovery occurred, assuming a linear PG increase in this limited time interval. The difference between the observed and the estimated true recovery for an individual is illustrated in the figure. The PG sample taken at 10 min is the first sample showing an increase of at least 20 mg/dL from the predose level, leading to an observed time to recovery of 10 min. Linear interpolation estimates the increase of 20 mg/dL to occur at 9 min for this individual. Using interpolated PG values, the median estimated true time to recovery for dasiglucagon was 8.7 min in the phase 2 trial and 9.0 to 9.3 min in phase 3 trials. These data provide further insight into the probable "true time to recovery" and confirm the consistent efficacy of dasiglucagon in the treatment of hypoglycemia.
The efficacy of dasiglucagon 0.6 mg, a glucagon analog stable in aqueous formulation, has been established versus placebo in previously reported trials in adults with type 1 diabetes mellitus. An ...integrated analysis was conducted to investigate efficacy in demographic and other subgroups. To allow as many individuals as possible in the evaluation, the analysis comprised data from 4 trials in adults, including 2 pivotal trials, an additional phase 3 trial, and a phase 2 trial. The trials were conducted under similar conditions with respect to design characteristics, such as target population, background therapy and treatment duration. All trials included efficacy assessments following insulin-induced hypoglycemia and showed consistent efficacy results across trials. The primary endpoint was time to plasma glucose (PG) recovery, defined as first PG increase ≥ 20 mg/dL after treatment initiation without need for rescue intravenous glucose. A total of 220 participants were exposed to dasiglucagon 0.6 mg across trials. Results of the integrated analysis are shown as a Forest plot of median time to PG recovery for dasiglucagon, including 95% confidence intervals by subgroup. In conclusion, the results showed that the efficacy of dasiglucagon was highly consistent across subgroups, with a median time to recovery from insulin-induced hypoglycemia of 10 minutes in most groups.
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