Endpoint HbA1c Research Articles

Study of age, sex and body mass index wise variation in C-peptide level among urban population of Northern part of Bihar

Background: Different factors regulate the insulin level in blood. Earlier C-peptide was considered as by product of insulin biosynthesis and its role in body seems to be negligible. C-peptide at low physiological concentrations mimics the effects of insulin. However, in the presence of elevated level of insulin concentrations concomitant raised level of C-peptide may blunt peripheral effects of insulin age. This study was carried out to verify the age, sex, and BMI wise variation in level of C-peptide among apparently healthy individual and its contribution in fine-tuning of the tissue’s metabolism under different physiological conditions. Methods: This is a prospective cross-sectional observational study. Estimation of serum c-peptide level was done by solid phase direct sandwich enzyme linked immunosorbent assay (ELISA) kit method. Glucose is estimated by Glucose oxidase peroxidase (GOD-POD) end point colorimetric method and HbA1C was estimated by ion exchange resin method (kit method). Result: Serum C-peptide level is significantly high in advance age and males in compared to younger age and females respectively. The mean level of serum C-peptide is higher in higher body mass index (BMI) group compared to lower, but this difference is statistically insignificant. Conclusions: In normal subjects, the level of C-peptide shows positive correlation with age and BMI. Males have higher level of C-peptide in comparison to females. Apart from these variation C-peptide contributes to different biological effects.

787-P: Glucose and Weight Outcomes Associated with Oral Semaglutide in the Real-World—Initial Results from the Association of British Clinical Diabetologists’ (ABCD) Audit

Semaglutide is the first glucagon like peptide-1 receptor agonist (GLP1-RA) available in an oral preparation. Weight and HbA1c outcomes with injectable semaglutide in the real-world are well established. The aim of this analysis is to assess weight and HbA1c response to oral semaglutide. Methods: Data were extracted from the secure online ABCD audit tool. Individuals were included if baseline and follow-up weight and/or HbA1c data were available. Change in HbA1c, body mass index (BMI) and weight from baseline was assessed using a multivariate linear regression model and change in the numbers achieving an endpoint HbA1c≤7.5% [58mmol/mol] were assessed using Chi2 tests in Stata 16. Results: Data were available for 350 individuals with baseline mean±SD HbA1c 9.2%±1.7 [76.6mmol/mol±18.3], weight 101.8kg±21.9, BMI 34.3kg/m2±6.9, median diabetes duration 11years (IQR 6-16) and age 59 years (IQR 51-68); 63.0% were male and 79.7% were white. Median follow-up was 0.5years (IQR 0.3-0.8). Significant reductions in HbA1c of 0.7% (95%CI 0.4, 0.9; P<0.001) [7.4mmol/mol; 95%CI 4.7, 10.0; P<0.001] were observed. Weight decreased by 3.3kg (95%CI 2.3, 4.3; P<0.001) and BMI fell by 1.1kg/m2 (95%CI 0.6, 1.6; P<0.001). Twice as many people achieved a HbA1c≤7.5% at follow-up compared to baseline (28.6% [52/182] vs 14.3% [26/182]) - this change was statistically significant (P<0.001). Conclusion: In the real-world, oral semaglutide is associated with statistically significant and clinically meaningful reductions in HbA1c, weight and BMI. The numbers achieving a HbA1c≤7.5% also increased. In the light of this, further data collection and analysis should be undertaken, including comparisons between oral and injectable GLP1-RAs and analysis of switches between them Disclosure T.S.J.Crabtree: Speaker's Bureau; Abbott Diabetes, Novo Nordisk, Lilly, Sanofi, Insulet Corporation. K.Adamson: None. S.Krishnasamy: Other Relationship; Novo Nordisk, Sanofi, Eli Lilly and Company, AstraZeneca. M.Khine: None. P.De: Speaker's Bureau; Novo Nordisk, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Takeda Canada, Daiichi Sankyo, Napp Pharmaceuticals Limited, Lilly Diabetes. R.Peter: None. R.E.Ryder: Other Relationship; Novo Nordisk, Speaker's Bureau; GI Dynamics, BioQuest. Funding Novo Nordisk

Metabolic bariatric surgery as a therapeutic option for patients with type 2 diabetes: A meta-analysis and network meta-analysis of randomized controlled trials.

To compare different types of metabolic surgery with non-surgical therapy for the treatment of type 2 diabetes (T2D). The present network meta-analysis (NMA) includes randomized clinical trials (duration ≥ 52 weeks) comparing different surgery techniques with non-surgical therapy in diabetes patients. The primary endpoints were endpoint HbA1c, body mass index (BMI) and diabetes remission. The secondary endpoints included fasting plasma glucose, lipid profile, blood pressure, arterial hypertension and dyslipidaemia remission, quality of life and surgical adverse events. Indirect comparisons of different types of surgery were performed by NMA. Mean and 95% confidence intervals for continuous variables, and the Mantel-Haenzel odds ratio for categorial variables, were calculated. The types of surgical procedure included laparoscopic adjustable gastric banding, Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), bilio-pancreatic diversion (BPD), greater curvature plication (GCP), one-anastomosis gastric bypass (OAGB) and Duodeno-Jejunal bypass. Thirty-six trials were included. Metabolic bariatric surgery (MBS) was associated with a significantly higher reduction of HbA1c, diabetes remission and BMI compared with medical therapy. In the NMA, a significant reduction of HbA1c was observed with OAGB and SG. Complete diabetes remission significantly increased with all surgical procedures in comparison with non-surgical therapy, except for GCP. In addition, only BPD, RYGB and OAGB were associated with a significant reduction of BMI. MBS is an effective option for the treatment of T2D in patients with obesity. Further long-term trials of appropriate quality are needed for assessing the risk-benefit ratio in some patient cohorts, such as those with a BMI of less than 35 kg/m2 and aged older than 65 years.

Efficacy and Safety of Ultra-Rapid Lispro in Younger and Older Patients with Type 2 Diabetes: Randomized Double-Blind PRONTO-T2D Study.

IntroductionUltra-rapid lispro (URLi) is a new prandial insulin lispro formulation. In the PRONTO-T2D study, URLi, in a basal-bolus regimen with glargine or degludec, was non-inferior to lispro (Humalog®) for HbA1c reduction and superior for postprandial glucose (PPG) control. We evaluated the efficacy and safety of URLi compared to lispro in younger versus older patients in PRONTO-T2D.MethodsPRONTO-T2D was a phase 3, 26-week, double-blind, treat-to-target study in people with type 2 diabetes. In this sub-group analysis, we compared URLi to lispro on the change from baseline in HbA1c and rate of level 2 hypoglycemia (< 54 mg/dl) in patients aged < 65 (N = 406) and ≥ 65 years (N = 267).ResultsAt baseline, patients < 65 versus ≥ 65 years had mean age of 54.9 versus 69.2 years and duration of diabetes 14.6 versus 19.4 years. Mean HbA1c at screening and randomization was 8.35 and 7.34%, respectively, in patients < 65 years, and 8.21 and 7.23%, respectively, in patients ≥ 65 years. At endpoint, mean HbA1c with URLi versus lispro was 6.92 versus 6.90%, respectively, in patients < 65 years and 6.89 versus 6.79%, respectively, in patients ≥ 65 years. URLi significantly reduced 1- and 2-h PPG excursions with a standardized meal test in both age groups: between-treatment differences at 1-h postmeal for younger and older patients was – 9.8 and – 15.1 mg/dl, respectively; and at 2-h postmeal, – 18.7 and – 15.1 mg/dl, respectively, all p < 0.05. Severe and nocturnal hypoglycemia were similar between groups. The relative rate (URLi/Humalog) of level 2 hypoglycemia was lower in older versus younger patients, with a significant treatment-by-age interaction observed. No differential treatment effects were noted for insulin dose, weight, and fasting and maximum glucose after the meal test.ConclusionsURLi, in a basal-bolus regimen, resulted in endpoint HbA1c < 7% and significantly lower PPG excursions compared to lispro in both age groups, with reduced level 2 hypoglycemia in older versus younger patients.Trial registrationClinicalTrials.gov, NCT03214380.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-022-01290-4.

718-P: Patients Achieving an HbA1c &amp;lt;5.7% with =5% Weight Loss and without Hypoglycemia: A Post Hoc Analysis of SURPASS 1 to 5

In the phase 3 SURPASS studies of tirzepatide (TZP) , a novel dual GIP/GLP-1 receptor agonist developed for the treatment of type 2 diabetes, 23%-62% of TZP-treated participants achieved a HbA1c &amp;lt;5.7% and 54%-88% achieving ≥5% weight loss. This post hoc analysis evaluated the proportion of participants who achieved the triple endpoint of HbA1c &amp;lt;5.7%, ≥5% weight loss, and no clinically significant or severe hypoglycemia. We compared the proportion of participants achieving the triple endpoint between the TZP (5, 10, or 15 mg) and respective comparator groups using the efficacy analysis dataset without rescue medication. HbA1c and weight were evaluated at the end of the treatment period at week 40 (SURPASS 1, 2, 5) or week 52 (SURPASS 3, 4) . Hypoglycemia included blood glucose level &amp;lt;54 mg/dL with symptoms or severe hypoglycemia at any time. Significantly more participants treated with any dose of TZP achieved the triple endpoint compared to placebo or active comparators in SURPASS 1-5 (Figure) . Of the participants treated with TZP 15 mg, 45%, 48%, 48%, 41%, 55% reached the triple endpoint compared to 1% with placebo, 15% with semaglutide 1 mg, 2% with degludec, 1% with glargine U100, and 1% with placebo, in SURPASS 1-5, respectively. Significantly more participants treated with TZP achieved a HbA1c &amp;lt;5.7% with ≥5% weight loss and without hypoglycemia compared to placebo, semaglutide 1 mg, or basal insulin. Disclosure A.Y. Cheng: Advisory Panel; Abbott, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Dexcom, Inc., Eli Lilly and Company, HLS Theraoeutics, Insulet Corporation, Janssen Pharmaceuticals, Inc., Medtronic, Novo Nordisk, Sanofi. Board Member; Type 1 Diabetes Think Tank Network. Speaker's Bureau; Bausch Health, Canada, Merck &amp; Co., Inc. Other Relationship; Diabetes Canada. I. Lingvay: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly, Mannkind, TARGET PharmaSolutions; Valeritas;; Altimmune; DataRevive; Click; Medscape Duke CRI; Janssen Pharma; Bayer; Intercept, Novo Nordisk, Sanofi, Zealand Pharma A/S. Consultant; Novo Nordisk. Research Support; NovoNordisk; Mylan; Merck, Sanofi. P. Choudhary: Advisory Panel; Abbott Diabetes, Lilly Diabetes, Medtronic. Research Support; Novo Nordisk. Speaker's Bureau; Dexcom, Inc., Glooko, Inc., Insulet Corporation, Sanofi. E. Gomez-Valderas: Employee; Lilly. Stock/Shareholder; Lilly. S. Allen: None. K.T. Ranta: Employee; Eli Lilly and Company. J.A. Levine: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. V. Thieu: None. Funding Eli Lilly and Company

Self-management in patients with type 2 diabetes: Group-based versus individual education. A systematic review with meta-analysis of randomized trails

AimPatient education is an essential component of the treatment of type 2 diabetes mellitus (T2DM). The present meta-analysis was aimed at verifying the efficacy of group-based versus individual education for self-management in patients with T2DM. Data synthesisA Medline and Embase search up to January 1st, 2021, was performed, including Randomized Controlled Trials (RCT) with duration>6 months, enrolling patients with T2DM and comparing individual-based with group-based educational programs. The primary outcome was endpoint HbA1c; secondary endpoints were lipid profile, body weight, blood pressure, patients’ adherence/knowledge, and quality of life. The weighed difference in means (WMD) and Mantel-Haenzel Odds Ratio (MH–OR), with 95% Confidence Interval (CI), were calculated.We retrieved 14 RCT. No significant between-group difference in HbA1c (WMD -0.39[-0.89; 0.09] mmol/mol, p = 0.11) was observed. At metaregression analyses, longer trial duration, higher baseline mean age and duration of diabetes, and lower baseline HbA1c were correlated with greater efficacy of group-based programs in reducing HbA1c. When analyzed separately, trials excluding insulin-treated patients showed a significant reduction of HbA1c in favor of group education. ConclusionsIn patients with T2DM, group education has similar efficacy as individual education on glucose control. Group programs are associated with an improved quality of life and patients’ knowledge. Prospero and OSF registrationID243149.

Ultra rapid lispro improves postprandial glucose control compared with lispro in patients with type 1 diabetes: Results from the 26-week PRONTO-T1D study.

AimsTo evaluate the efficacy and safety of ultra rapid lispro (URLi) versus lispro in adults with type 1 diabetes in a 26‐week, treat‐to‐target, phase 3 trial.Materials and methodsAfter an 8‐week lead‐in to optimize basal insulin glargine or degludec, patients were randomized to double‐blind mealtime URLi (n = 451) or lispro (n = 442), or open‐label post‐meal URLi (n = 329). The primary endpoint was change from baseline glycated haemoglobin (HbA1c) to 26 weeks (non‐inferiority margin 0.4%), with multiplicity‐adjusted objectives for postprandial glucose (PPG) excursions after a meal test.ResultsBoth mealtime and post‐meal URLi demonstrated non‐inferiority to lispro for HbA1c: estimated treatment difference (ETD) for mealtime URLi −0.08% [95% confidence interval (CI) −0.16, 0.00] and for post‐meal URLi +0.13% (95% CI 0.04, 0.22), with a significantly higher endpoint HbA1c for post‐meal URLi versus lispro (P = 0.003). Mealtime URLi was superior to lispro in reducing 1‐ and 2‐hour PPG excursions during the meal test: ETD −1.55 mmol/L (95% CI −1.96, −1.14) at 1 hour and − 1.73 mmol/L (95% CI −2.28, −1.18) at 2 hours (both P < 0.001). The rate and incidence of severe, documented and postprandial hypoglycaemia (<3.0 mmol/L) was similar between treatments, but mealtime URLi demonstrated a 37% lower rate in the period >4 hours after meals (P = 0.013). Injection site reactions were reported by 2.9% of patients on mealtime URLi, 2.4% on post‐meal URLi, and 0.2% on lispro. Overall, the incidence of treatment‐emergent adverse events was similar between treatments.ConclusionsThe results showed that URLi provided good glycaemic control, with non‐inferiority to lispro confirmed for both mealtime and post‐meal URLi, while superior PPG control was demonstrated with mealtime dosing.

1046-P: Effect of Age on HbA1c, Postprandial Glucose (PPG) Control, and Hypoglycemia in Patients with T2D Treated with Ultra-Rapid Lispro (URLi) or Humalog: PRONTO-T2D

URLi is a novel prandial insulin lispro formulation developed to more closely match physiological insulin secretion. PRONTO-T2D, a Phase 3, double-blind, treat-to-target study in pts with T2D, showed URLi, in a basal-bolus regimen with glargine or degludec, was non-inferior for HbA1c with superior PPG control vs. Humalog. Subgroup analyses were performed in pts &amp;lt;65 vs. ≥65 years. Baseline characteristics were similar except age and duration of T2D (Table 1). With 26 weeks of study treatment, HbA1c improved in both treatment/age groups with endpoint mean HbA1c 6.8-6.9%. URLi significantly reduced 1- and 2-hour PPG excursions with standardized meal tests vs. Humalog in both age groups. Insulin dosing was not significantly different. Severe hypoglycemia incidence was low. While there was no treatment difference in documented hypoglycemia (glucose &amp;lt;54 mg/dL), relative rate (URLi/Humalog) was lower in pts ≥65 vs. &amp;lt; 65 years, with a significant treatment-by-age interaction. Nocturnal hypoglycemia was not significantly different between groups. Incidence of overall treatment-emergent adverse events was similar between treatment/age groups. URLi in a basal-bolus regimen resulted in endpoint HbA1c &amp;lt;7% and significantly lower PPG excursions vs. Humalog in both age groups, with reduced documented hypoglycemia in older vs. younger pts. Disclosure A.M. Chang: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. T. Hardy: Other Relationship; Self; Eli Lilly and Company. Q. Zhang: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Funding Eli Lilly and Company

The Benefit of Insulin Degludec/Liraglutide (IDegLira) Compared With Basal-Bolus Insulin Therapy is Consistent Across Participant Subgroups With Type 2 Diabetes in the DUAL VII Randomized Trial.

Insulin degludec/liraglutide (IDegLira) results in glycated hemoglobin (HbA1c) levels comparable with basal-bolus (BB) therapy. Here, we assessed the effect of once-daily IDegLira compared with BB (once-daily insulin glargine 100 U/mL and insulin aspart ≤4 times/day) across subgroups with varying characteristics. DUAL VII trial participants (type 2 diabetes [T2D], HbA1c 53-86 mmol/mol [7.0%-10.0%]) were subgrouped post hoc based on the following baseline characteristics: HbA1c (≤58.5, >58.5 to ≤69.4, and >69.4 mmol/mol; ≤7.5%, >7.5 to ≤8.5%, and >8.5%), body mass index (<30, ≥30 to <35, and ≥35 kg/m2), age (18 to <65 and ≥65 years), duration of diabetes (≥0 to 10 and ≥10 years), total pretrial daily basal insulin dose (20 to <30, ≥30 to <40, and ≥40 to ≤50 U), and fasting plasma glucose (<7.2 mmol/L/<130 mg/dL and ≥7.2 mmol/L/≥130 mg/dL). Compared with BB, and in all subgroups, IDegLira treatment consistently gave similar HbA1c reductions, less severe or blood glucose-confirmed hypoglycemia, lower end-of-trial (EOT) total daily insulin dose, and weight loss. In all subgroups, mean EOT HbA1c was ≤53 mmol/mol (≤7.0%). The greatest HbA1c reduction occurred in the highest baseline HbA1c subgroup. Overall, mean EOT daily insulin dose was 0.43 to 0.52 U/kg with IDegLira and 0.74 to 1.07 U/kg with BB. More participants achieved the triple composite endpoint (HbA1c <53 mmol/mol [<7.0%] without weight gain or hypoglycemia) with IDegLira vs BB across the baseline HbA1c subgroups (≤58.5 mmol/mol [44.6% vs 7.0%], >58.5 to ≤69.4 mmol/mol [41.1% vs 8.3%], and >69.4 mmol/mol [23.8% vs 3.4%]). These results support initiating IDegLira in patients with varying baseline characteristics and uncontrolled T2D on basal insulin. NCT02420262.

How conclusive is the CONCLUDE trial?

The development of basal insulin analogues has reduced the risk of hypoglycaemia in insulin-treated individuals with type 2 diabetes. Insulin degludec and insulin glargine 300U/ml (glargine U300) represent an evolution of basal insulin analogues, both of them reducing the risk of hypoglycaemia as compared with that associated with glargine U100. However, whether degludec and glargine U300 are equivalent with respect to glycaemic control and risk of hypoglycaemia remains to be fully ascertained. In the CONCLUDE trial, 1609 individuals with type 2 diabetes were randomised to either degludec 200U/ml (degludec U200) or glargine U300. In this issue of Diabetologia (https://doi.org/10.1007/s00125-019-05080-9) the investigators report that during the maintenance period, HbA1c improved to a similar extent in the two groups with no significant difference in the rate of overall hypoglycaemia (the primary endpoint of the study), while rates of nocturnal symptomatic and severe hypoglycaemia (secondary endpoints) were lower with degludec U200 than with glargine U300. These results, although of great interest to the clinician, need to be carefully interpreted as they cannot be considered as conclusive. First, the primary endpoint was not met and, therefore, analyses of secondary endpoints remain exploratory. Even assuming that degludec is superior to glargine in reducing the risk of hypoglycaemia, the mechanism(s) accounting for such an advantage remain elusive and potential differences in pharmacokinetics and pharmacodynamics difficult to appreciate because of methodological issues. The study design had to be amended because of lack of reliability of the glucometers initially used in the trial, particularly in the low blood glucose ranges, so the potential implications of these changes in the subsequent conduct of the trial cannot be excluded. Finally, comparison with the BRIGHT trial, the only other available head-to-head study, is complicated by differences between the two studies in the primary endpoint (HbA1c reduction vs reduction of the risk of hypoglycaemia), study population (insulin-experienced vs insulin-naive) and concomitant glucose-lowering medications. In spite of all this, CONCLUDE teaches us an important lesson regarding the need, particularly in the clinical setting, to monitor the reliability of the glucometers the diabetic individual uses to adjust his/her insulin dose. Insufficient precision or inappropriate use of the glucometer can easily offset any minute advantage a new insulin can offer with respect to glycaemic control and risk of hypoglycaemia.

Investigation of early signs of systolic and diastolic dysfunction among persons with type 1 diabetes

BackgroundPersons with type 1 diabetes have a higher risk to develop heart failure than the general population, and the mechanism behind the increased risk is unclear. In epidemiological studies with...

Impact of baseline characteristics and beta-cell function on the efficacy and safety of subcutaneous once-weekly semaglutide: A patient-level, pooled analysis of the SUSTAIN 1-5 trials.

AimTo evaluate the impact of relevant patient‐level characteristics on the efficacy and safety of subcutaneous, once‐weekly semaglutide in subjects with type 2 diabetes.Materials and MethodsExploratory post hoc analyses of pooled SUSTAIN 1‐5 (phase 3a) randomized, controlled trials examined the change from baseline in HbA1c and body weight (BW), and the proportions of subjects achieving the composite endpoint (HbA1c < 7.0% [53 mmol/mol]), without weight gain or severe/blood glucose‐confirmed symptomatic hypoglycaemia at week 30 with semaglutide (0.5/1.0 mg) across clinically relevant patient subgroups: baseline HbA1c (≤7.5%, >7.5%‐8.0%, >8.0%‐8.5%, >8.5%‐9.0% and > 9.0%), background medications, diabetes duration and pancreatic beta‐cell function.ResultsMean HbA1c (% point) reductions increased from lowest to highest HbA1c subgroups (−0.9%, −1.2%,‐1.5%, −1.7% and −2.3% [effect of subgroup within treatment: P = 0.247] for semaglutide 0.5 mg, and −1.1%, −1.4%, −1.9%, −2.1% and −2.7% [P = 0.045] for semaglutide 1.0 mg), with mean HbA1c ranges at week 30 of 6.3%‐7.3% and 6.1%‐6.9%, respectively. The corresponding BW reductions generally decreased with increasing baseline HbA1c (−4.4, −3.9, −3.9, −3.3 and −2.9 kg [P = 0.004], and −6.4, −5.9, −5.2, −4.5 and −4.8 kg [P < 0.001], respectively). HbA1c and BW reductions were consistently greater for semaglutide 1.0 mg versus 0.5 mg across background medication, diabetes duration and pancreatic beta‐cell function subgroups. Adverse events with semaglutide were consistent with the glucagon‐like peptide‐1 receptor agonist class, with gastrointestinal events the most common.ConclusionsSemaglutide was consistently efficacious across the continuum of diabetes care in a broad spectrum of patient subgroups with a range of clinical characteristics.

Fasting C-peptide, a biomarker for hypoglycaemia risk in insulin-naïve people with type 2 diabetes initiating basal insulin glargine 100 U/mL.

To examine the relationship between baseline fasting C-peptide (FCP) and outcomes in insulin-naïve people with type 2 diabetes initiating basal insulin glargine 100 U/mL (Gla-100). Post hoc pooled analysis of nine randomized, treat-to-target trials in patients with type 2 diabetes inadequately controlled on oral antihyperglycaemic drugs initiating once-daily Gla-100. Participants (n = 2165) were stratified at baseline according to FCP (≤0.40, >0.40-1.20, >1.20-2.00, >2.00 nmol/L). Glycaemic control, body weight, insulin dose and hypoglycaemia were determined at 24 weeks. At baseline low FCP levels were associated with longer known diabetes duration, lower body mass index and higher fasting plasma glucose (FPG). Following Gla-100 introduction, the mean HbA1c reduction at week 24 was similar in all four FCP groups, albeit fewer people in the lowest FCP group achieved HbA1c <7.0% versus FCP groups >0.40 nmol/L. By contrast, FPG reduction and proportion reaching FPG ≤5.6 mmol/L were greatest in the lowest FCP group, diminishing at higher FCP levels. Gla-100 dose at week 24 was lowest in the ≤0.40 nmol/L FCP group and highest in the >1.20 nmol/L FCP group. Incidence and event rate of overall, nocturnal and severe hypoglycaemia were higher at week 24 in groups with lower FCP levels. In multivariable regression analysis baseline FCP, concomitant sulphonylurea use and endpoint HbA1c were strong predictors of hypoglycaemia. FCP levels identified patients with type 2 diabetes experiencing different responses to basal insulin Gla-100. A low FCP identifies a markedly insulin-deficient, insulin-sensitive subgroup/phenotype with an enhanced risk of hypoglycaemia, which requires a low initial basal insulin dose, cautious titration and earlier addition of prandial glucose-lowering therapy.

Impact of technology on glycaemic control in type 2 diabetes: A meta-analysis of randomized trials on continuous glucose monitoring and continuous subcutaneous insulin infusion.

To conduct a meta-analysis to assess the effect of continuous subcutaneous insulin infusion (CSII), continuous glucose monitoring (CGM), and the combination of the two, on glycaemic control in type 2 diabetes. The analysis included randomized clinical trials comparing CSII with multiple daily injections (MDI) in people with type 2 diabetes, as well as studies comparing CGM or flash glucose monitoring (FGM) with self-monitoring of blood glucose (SMBG), with a duration of at least 12 weeks, identified in Medline or clinicaltrials.gov. The principal endpoint was glycated haemoglobin (HbA1c) at the end of the trial. Mean and 95% confidence intervals (CIs) for HbA1c and Mantel-Haenzel odds ratios for severe hypoglycaemia were calculated, using random-effect models. The retrieved trials showed a significant heterogeneity (I2 = 90%). The difference in HbA1c between CSII and MDI was not statistically significant (-0.26% [95% CI -0.74;0.22]; P = .29). The difference in endpoint HbA1c between CGM and SMBG was marginally significant (-0.24 [95% CI -0.49;0.00]; P = .05), and CGM was possibly associated with a lower hypoglycaemic risk. Only one trial explored the effect of FGM, as compared with SMBG, on HbA1c in type 2 diabetes, finding no difference across groups (at study end: 8.4% ± 0.8% vs 8.3% ± 1.1% with FGM and SMBG, respectively). Conversely, FGM was associated with an improvement in quality of life and with a lower incidence of hypoglycaemic events. The small number of retrieved trials indicates that the results should be interpreted with caution. The analysis showed that CSII, CGM and FGM provide only small benefits compared with MDI (on either HbA1c, hypoglycaemic risk or quality of life) in insulin-treated people with type 2 diabetes.

&lt;p&gt;Cost–benefit comparison of liraglutide and sitagliptin in the treatment of type 2 diabetes in Thailand&lt;/p&gt;

AimLiraglutide, a once-daily subcutaneous glucagon-like peptide-1 (GLP-1) agonist, is approved for treatment of hyperglycemia in patients with type 2 diabetes mellitus (T2DM). For patients with established cardiovascular diseases, liraglutide has also been shown to reduce major cardiovascular events. However, its cost is relatively higher than other oral antidiabetic drugs. This study aims to compare the costs and benefits of liraglutide vs sitagliptin, in treating T2DM in Thailand.MethodsThis study consists of two parts. In part 1, the cost of keeping T2DM under control per patient (HbA1c<7.0% with no reported hypoglycemia and no body weight gain) with liraglutide (1.2 and 1.8 mg daily) was compared with using sitagliptin (100 mg daily). Costs were based on Thai local data. Clinical outcomes were based on head-to-head randomized controlled trials. Part 2 estimated the cost-per-controlled patient, based on major cardiovascular outcomes (cardiovascular death, nonfatal myocardial infarction, non-fatal stroke). Economic benefit was calculated as the reduction in cardiovascular outcomes.ResultsIn Thailand, liraglutide (1.8 mg daily) costs 7.37-times more than sitagliptin 100 mg. The cost per patient achieving a composite clinical endpoint (HbA1c<7.0%, with no weight gain and no hypoglycemic events) in patients with T2DM receiving liraglutide 1.8 mg is 2.80-times higher than patients receiving sitagliptin 100 mg. When cardiovascular benefits (reduced composite endpoint of major cardiovascular events, ie, cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke) were taken into account, it was found that liraglutide had lower cost than sitagliptin, resulting in estimated savings of 20,085 THB (620 USD) per patient per year.ConclusionThe clinical benefits of liraglutide (HbA1c<7.0%, no hypoglycemia, no weight gain, reduced cardiovascular outcomes) partly offset its high price. Therefore, liraglutide should be considered as an appropriate treatment alternative to sitagliptin, particularly for T2DM patients with high cardiovascular risks.

1134-P: Efficacy of iGlarLixi in Adults with Type 2 Diabetes Inadequately Controlled on Two or More Oral Antidiabetic Agents

LixiLan-O, a randomized, 30-week, open-label study compared the fixed-ratio combination of insulin glargine/lixisenatide (iGlarLixi) with insulin glargine (iGlar) or lixisenatide in patients inadequately controlled on metformin alone or combined with a second OAD. This exploratory subgroup analysis examines the efficacy and safety of iGlarLixi vs. iGlar in patients with baseline HbA1c ≥8.0% receiving metformin plus a second OAD at screening; the second OAD was a sulfonylurea in 93.8% of patients. Mean age was 59.2 years, mean BMI was 31.5 kg/m2, mean diabetes duration was 10.0 years, and mean duration of second OAD use was 4.5 years. Compared with iGlar alone, the iGlarLixi-treated group demonstrated greater mean reductions from baseline in HbA1c, 2-h PPG, and weight, greater proportions achieving HbA1c &amp;lt;7.0%, or a composite endpoint of HbA1c &amp;lt;7.0% with no weight gain (Table). There were no differences between the groups in change in FPG, or in insulin dose at Week 30 (40.7 vs. 40.2 U/day, respectively; p=0.8664). Incidences of documented symptomatic hypoglycemia (plasma glucose ≤70 mg/dL) were similar between groups (29.0% and 27.9%, respectively). Patients in this difficult-to-treat subgroup with advanced T2D and higher baseline HbA1c achieved better glycemic control without increased risk of hypoglycemia when intensified with iGlarLixi compared with iGlar. Disclosure N. Skolnik: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., GlaxoSmithKline plc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Mylan, Sanofi, Teva Pharmaceutical Industries Ltd. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., GlaxoSmithKline plc., Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. E. Niemoeller: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. E. Souhami: Employee; Self; Sanofi Research &amp; Development. L. Meneghini: Advisory Panel; Self; AstraZeneca, Novo Nordisk Inc., Sanofi-Aventis. Consultant; Self; Sanofi-Aventis. Other Relationship; Self; American Diabetes Association. Funding Sanofi

1014-P: Relationship between Glycemic Control and Weight Loss with Once-Weekly Efpeglenatide in Uncontrolled Type 2 Diabetes: A Subanalysis of EXCEED 203

Efpeglenatide (EFPEG) is a long-acting GLP-1 RA, administered by once-weekly (QW) subcutaneous injection, currently being developed to improve glycemic control in patients with T2D. EXCEED 203 (NCT02057172), a 12-week study of EFPEG (0.3, 1, 2, 3, or 4 mg QW) compared with placebo (PBO) and referenced to open-label liraglutide 1.8 mg in uncontrolled T2D (naïve/metformin monotherapy), found significantly improved HbA1c for all doses of EFPEG ≥1 mg, and reductions in body weight for EFPEG 3 and 4 mg. This exploratory subanalysis investigated any potential relationship between glycemic control and weight loss effects observed in EXCEED 203. At all EFPEG doses ≥1 mg and in two combined populations (low-dose group: EFPEG 1 and 2 mg; high-dose group: EFPEG 3 and 4 mg) vs. PBO, greater proportions of patients significantly achieved the composite endpoint of HbA1c &amp;lt;7% and weight loss &amp;gt;3 kg (p&amp;lt;0.05 for all; Table). Linear regression analysis revealed no correlation between change in HbA1c and change in body weight throughout the study for all EFPEG doses ≥1 mg. EFPEG was well tolerated with adverse events mirroring those known for GLP-1 RAs. In conclusion, EFPEG was associated with greater proportions of patients achieving the composite endpoint of HbA1c &amp;lt;7% and weight loss &amp;gt;3 kg vs. PBO without evidence that the glucose-lowering effects of EFPEG were dependent on weight loss. Disclosure J. Rosenstock: Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Genentech, Inc., GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Melior Pharmaceuticals, Inc., Bukwang Pharm. Co., Ltd., Merck &amp; Co., Inc., Oramed Pharmaceuticals, PegBio Co., Ltd., Pfizer Inc. Other Relationship; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. C. Morales: Other Relationship; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi. U. Wendisch: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Eli Lilly and Company, Kowa Pharmaceutical Europe Co. Ltd., Lexicon Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S. Stock/Shareholder; Self; Novartis AG, Novo Nordisk A/S. G.E. Dailey: Research Support; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi US. Speaker's Bureau; Self; Sanofi US. M.E. Trautmann: Consultant; Self; CeQur Corporation, Hanmi Pharm. Co., Ltd., Intarcia Therapeutics, Inc., Oramed Pharmaceuticals, ProSciento, Servier. Stock/Shareholder; Self; Lilly Diabetes. M. Hompesch: Stock/Shareholder; Self; ProSciento. I. Choi: Employee; Self; Hanmi Pharm. Co., Ltd. J. Kang: Employee; Self; Hanmi Pharm. Co., Ltd. J.A. Stewart: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. I. Ogbaa: Stock/Shareholder; Self; Lexicon Pharmaceuticals, Inc. Other Relationship; Self; Sanofi. C.H. Sorli: Employee; Self; Sanofi. K. Yoon: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Novo Nordisk Inc. Speaker’s Bureau; Self; Takeda Pharmaceutical Company Limited. Funding Hanmi Pharmaceutical, Co., Ltd.; Sanofi

217-OR: Islet Transplantation vs. Standard of Care for Type 1 Diabetes Complicated by Severe Hypoglycemia from the Collaborative Islet Transplant Registry (CITR) and T1D Exchange (T1DX) Registry

Islet transplantation is an emerging treatment for T1D, in particular for those with long standing disease experiencing severe hypoglycemia events (SHE). A phase 3 trial of islet transplantation in T1D complicated by SHE demonstrated &amp;gt; 80% of islet recipients achieved HbA1c &amp;lt; 7.0% and absence of SHE at 1 year. To better understand the long-term benefit for glycemic control and risk of immunosuppression to kidney function associated with islet transplantation vs. standard of care, we selected patients from CITR with at least one SHE in the year prior to transplant, and compared them to patients from T1DX with at least one SHE in the prior year and followed over 5 years. The cohorts from CITR (n = 58) and T1DX (n = 213) were aged 42 ± 9 and 43 ± 17 with disease duration 29 ± 10 and 26 ± 15 years (P &amp;lt; 0.01) and experienced 5 ± 11 and 2 ± 1 SHE (P &amp;lt; 0.01) in the year prior to baseline with HbA1c 7.3 ± 1.0 vs. 7.8 ± 1.5 (P &amp;lt; 0.001). Mean HbA1c decreased to 6.3% vs. ranging 7.8-7.6% over 5 years (P &amp;lt; 0.001), and the % experiencing recurrent SHE was less in CITR than T1DX (P &amp;lt; 0.01), such that 78-77% vs. 23-28% met the primary endpoint of HbA1c &amp;lt; 7.0% and absence of SHE (P &amp;lt; 0.001). Insulin requirements were slightly less at baseline in CITR than T1DX (0.52 ± 0.14 vs. 0.64 ± 0.31 U/kg/d; P &amp;lt; 0.001), and decreased to 0.06-0.17 vs. remaining 0.66-0.56 U/kg/d over 5 years (P &amp;lt;0.001) with 80-48% insulin independent in CITR. GFR was 92 ± 17 and 90 ± 29 ml/min/1.73 m2 at baseline, and decreased to 83-78 vs. 87-81 ml/min/1.73 m2 over 5 years (P &amp;lt; 0.001). These data demonstrate long-term durability of islet transplantation to achieve near-normal glycemic control in the absence of SHE more often than that observed with standard of care delivered by specialized diabetes practice. Initial reduction in GFR observed during the first-year post-transplant may be attributable to the initiation of immunosuppression, but was not associated with further decline during 5 year follow-up. Disclosure M.R. Rickels: None. N.C. Foster: None. C.M. Ballou: None. B.J. Hering: Other Relationship; Self; Diabetes-Free, Inc. R. Alejandro: None. R. Beck: Other Relationship; Self; Abbott Laboratories, Ascensia Diabetes Care, Bigfoot Biomedical, Dexcom, Inc., Insulet Corporation, Lilly Diabetes, Roche Diabetes Care, Tandem Diabetes Care. K. Miller: None. F.B. Barton: None. Funding National Institutes of Health; Leona M. and Harry B. Helmsley Charitable Trust

Effect of whole-grain plant-based diet on the diabetes mellitus type 2 features in newly diagnosed patients: a pilot study

Fifteen diabetic patients, with a duration of 4.9 months with diabetes and an average age of 49.6 ± 8.6 years, participated in a pilot study for 12 weeks to assess the effect of plant-based diet on their diabetes features. Participants were 2 females and 13 males and their baseline measurements were 30.2 ±5.4 kg/m2, 189.2 ± 76.3 mg/dL and 9.4 ± 2.5% for body mass index [BMI], fasting blood glucose [FBG] and HbA1c, respectively. Participant’s adherence to the dietary programme on a scale of 0–10 was 8 ± 1.5. Their endpoint BMI, FBG and HbA1c were 28.7 ± 4.3 kg/m2, 102.6 ± 19.8 mg/dL and 6.2 ± 0.8%, respectively. Weight loss was significantly correlated with baseline body weight, baseline BMI and duration in diabetes, while baseline fasting blood glucose was correlated with baseline and endpoint HbA1c [p < 0.01]. However, it was not significantly correlated with endpoint body weight [p < 0.08] and BMI [p < 0.018]. This study has shown that management of body parameters [weight and BMI] through diet such as plant-based diet has resulted in significant reduction in diabetes parameters such as FBG and HbA1c. A larger number of participants are recommended in similar type of studies to have solid conclusions.

Lower Hypoglycemia Rates with Insulin Glargine 300 U/mL (Gla-300) vs. Insulin Degludec 100 U/mL (IDeg-100) in Insulin-Naïve Adults with T2DM on Oral Antihyperglycemic Therapy ± GLP-1RA—The BRIGHT Randomized Study

This 24-week open-label, treat-to-target trial (NCT02738151) investigated the efficacy and safety of Gla-300 vs. IDeg-100 in insulin-naïve T2DM, inadequately controlled on oral antihyperglycemic drugs ± GLP-1 RAs. Non-inferiority of Gla-300 vs. IDeg-100 was demonstrated for the primary endpoint (HbA1c change, baseline to week 24). Here we analyzed hypoglycemia by treatment period; day 1 to week 24 (full study period), day 1 to week 12 (titration period) and week 13 to week 24 (maintenance period). Incidence of confirmed [≤70 mg/dL] or severe hypoglycemia at any time of day (24 h) was lower with Gla-300 vs. IDeg-100 (odds ratio 0.74 [95% confidence interval: 0.57 to 0.97]) during the titration period but was similar at any time of day (24 h) or at night (00:00-05:59 h) during the maintenance and full study periods. Annualized rates of hypoglycemia (Figure) were lower with Gla-300 vs. IDeg-100 during the full study period, particularly over the titration period, despite higher final daily doses of Gla-300 vs. IDeg-100 (0.54 and 0.43 U/kg from starting doses 0.2 U/kg and 10 U/day [0.12 U/kg], respectively). Gla-300 resulted in similar incidence but lower rates of hypoglycemia, particularly during the titration period, with comparable glycemic control vs. IDeg-100 in insulin-naïve people with T2DM ± GLP-1 RA. Disclosure G.B. Bolli: Speaker's Bureau; Self; Menarini Group, Sanofi. Research Support; Self; Sanofi. A. Cheng: Advisory Panel; Self; Abbott. Speaker's Bureau; Self; Abbott. Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Merck &amp; Co., Inc.. Speaker's Bureau; Self; Merck &amp; Co., Inc.. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Consultant; Self; Takeda Canada Inc.. Research Support; Self; Sanofi, Boehringer Ingelheim GmbH. Z. Bosnyak: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. E. Boelle-Le Corfec: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. A.M. Cali: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. X. Wang: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. J.P. Frias: Research Support; Self; AbbVie Inc., Allergan, Amgen Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company. Consultant; Self; CeQur Corporation. Research Support; Self; Cirius Therapeutics, AstraZeneca, Calibra Medical, Elcelyx Therapeutics, Inc.. Consultant; Self; Elcelyx Therapeutics, Inc.. Research Support; Self; Eli Lilly and Company, Genentech, Inc., Ionis Pharmaceuticals, Inc., ICON plc., Janssen Pharmaceuticals, Inc.. Consultant; Self; Johnson &amp; Johnson Diabetes Institute, LLC.. Research Support; Self; Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc.. Consultant; Self; Ligand Pharmaceuticals, Inc.. Research Support; Self; Merck &amp; Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Pfizer Inc., Sanofi. Consultant; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; Theracos, Inc. R. Roussel: Advisory Panel; Self; AbbVie Inc., Abbott, Eli Lilly and Company, Sanofi, Novo Nordisk A/S, AstraZeneca. Speaker's Bureau; Self; Servier. Consultant; Self; Bayer AG. Advisory Panel; Self; Merck Sharp &amp; Dohme Corp.. Research Support; Self; Amgen Inc., Sanofi, Novo Nordisk A/S, Danone Research. Stock/Shareholder; Self; Iriade. Advisory Panel; Self; Physiogenex S.A.S. J. Rosenstock: Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Advisory Panel; Self; Sanofi. Consultant; Self; Sanofi. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Intarcia Therapeutics, Inc.. Consultant; Self; Intarcia Therapeutics, Inc.. Research Support; Self; Merck &amp; Co., Inc., Pfizer Inc., Sanofi, Novo Nordisk Inc., Bristol-Myers Squibb Company, Eli Lilly and Company, Intarcia Therapeutics, Inc., Genentech, Inc..