bluuebunny/crossref_metadata_2025 huggingface dataset:
796-P: Glucose-Lowering Drugs and Risk of COPD Exacerbations in Adults with Type 2 Diabetes
Authors: RAY AVIK , PAIK JULIE M. , FELDMAN WILLIAM B. , KATTINAKERE SREEDHARA SUSHAMA , WEXLER DEBORAH J. , PATORNO ELISABETTA
Published: June 2024

Introduction & objective: Recent studies suggest a possible therapeutic role of glucose-lowering drugs for chronic obstructive pulmonary disease (COPD). We compared sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP1-RA), and dipeptidyl peptidase 4 inhibitors (DPP4i) regarding the risk of COPD exacerbations.

Methods: Using data from a US commercial claims database (2013-2023), we identified 7,472 pairs of 1:1 propensity score (PS) matched adults aged >=40 years with type 2 diabetes (T2D) initiating SGLT2i or DPP4i, 7,600 pairs initiating GLP1-RA or DPP4i, and 10,187 pairs initiating SGLT2i or GLP1-RA. We estimated HRs and 95% CIs for the risk of a COPD exacerbation, defined as an inpatient COPD diagnosis (severe exacerbation) or an outpatient COPD diagnosis and a filled prescription of oral prednisone (moderate exacerbation), adjusting for 91 covariates.

Results: The risk of moderate or severe COPD exacerbation was lower in the SGLT2i (HR, 0.79; 95% CI, 0.71-0.88) and the GLP1-RA (HR, 0.79; 95% CI, 0.71-0.88) groups compared with DPP4i, and was similar between SGLT2i and GLP1-RA (HR, 0.93; 95% CI, 0.83-1.03), over a median follow-up of 4.3 months on treatment (Table). Results were consistent in subgroup analyses based on asthma history.

Conclusion: SGLT2i and GLP1-RA were associated with reduced risk of moderate or severe COPD exacerbations, compared to DPP4i in adults with T2D.

Disclosure

A. Ray: None. J.M. Paik: None. W.B. Feldman: None. S. Kattinakere Sreedhara: None. D.J. Wexler: Other Relationship; Novo Nordisk. E. Patorno: Research Support; Boehringer-Ingelheim, Food and Drug Administration (FDA), National Institutes of Health, Patient-Centered Outcomes Research Institute.
801-P: TRIM—Teen Obesity and GLP-1 Receptor Agonists—Insights from a Systematic Review, Meta-analysis, and Drug-Wise Network Meta-analysis
Authors: AAQIB SHAMIM MUHAMMAD , RASTOGI ASHU , SINGH SURJIT , CHENCHULA SANTENNA , GANESH VENKATA , TIWARI KRISHNA , BABU VARTHYA SHOBAN , DWIVEDI PRADEEP , SHUKLA RAVINDRA , RAO PRIYANKA , SATAPATHY PRAKISINI , PATIL AMOL , AMIN ULFAT , ROY TULI , P GANDHI ARAVIND , SAH RANJIT
Published: June 2024

Introduction & Objective: Obesity in adolescents is linked with adverse health outcomes. GLP1RAs have provided promising but conflicting results. We summarised the evidence for GLP1RAs in adolescents with obesity for weight-related outcomes.

Methods: We screened PubMed, Cochrane, Scopus, and Web of Science till 2023/04/29 for eligible RCTs. We compared GLP1RAs vs placebo, and then individual GLP1RAs in a network meta-analysis. We used a random effects model to account for the clinical heterogeneity, used the clinically more interpretable prediction intervals (PI), and assessed study quality and evidence quality.

Results: We identified 12 RCTs mostly at a low risk of bias. GLP1RAs led to a greater weight reduction [-4.21 kg; 95% CI -7.08 to -1.35; 95% PI -14.44 to 6.01; 11 RCTs; 818 participants; high quality evidence]. There is also reduction in BMI and waist circumference. The results are consistent in subgroup analyses for coexisting T2D. There is greatest efficacy with Semaglutide followed by Exenatide, Liraglutide, and Lixisenatide [Figure].

Conclusion: GLP1RAs reduce weight-related outcomes in adolescents with Semaglutide being the most efficacious. RCTs with direct comparisons, pragmatic study design, longer follow-up (to generate or verify safety signals), and adiposity-related outcomes are needed to further guide the usage and choice of GLP1RAs.

Disclosure

M. Shamim: None. A. Rastogi: None. S. Singh: None. S. Chenchula: None. V. Ganesh: None. K. Tiwari: None. S. Varthya: None. P. Dwivedi: None. R. Shukla: None. P. Rao: None. P. Satapathy: None. A. Patil: None. U. Amin: None. T. Roy: None. A. Gandhi: None. R. Sah: None.
802-P: A New Dawn beyond Basal Insulin? Dose-Response Meta-analysis for Efficacy and Safety of Tirzepatide Compared with Basal Insulin in Uncontrolled Diabetes Mellitus
Authors: AAQIB SHAMIM MUHAMMAD , DWIVEDI PRADEEP , AGGARWAL PIYUSH , DWIVEDI RAKHI , ANIL ABHISHEK , SARAVANAN ASWINI , TIWARI KRISHNA , DODIYA RAKESH P. , YADAV ISHA , SUKHIJA SANCHI , BABU VARTHYA SHOBAN , SHUKLA RAVINDRA , SINGH SURJIT , SINGH KULDEEP
Published: June 2024

Introduction & Objective: Insulin is the mainstay for uncontrolled type 2 diabetes mellitus (T2D) but is associated with hypoglycemia and weight gain. Tirzepatide is a first-in-class dual incretin GLP-1/GIP analog. We assessed the efficacy and safety of Tirzepatide compared to basal insulin for uncontrolled T2D.

Methods: We searched PubMed, Scopus, and CENTRAL till 2023/08/02 for relevant RCTs. We compared Tirzepatide 15mg once weekly with basal insulin, and then various doses after confirming dose-response linearity by Wald’s test. Then, we graded the evidence quality. Protocol: CRD42023450278 [PROSPERO]

Results: We identified 4,339 patients from 3 RCTs. Tirzepatide 15mg has a greater reduction in HbA1c [-1.23%, -1.53 to -0.93] compared to basal insulin. The 95% prediction interval for expected reduction in clinical practice is -5.04 to 2.58. More patients had >5% weight loss [RR 13.75, 9.91 - 19.09] and adverse events [RR 1.95, 1.66 - 2.30], but not serious adverse events [RR 0.78, 0.53 - 1.16]. There is considerable dose-dependent improvement in efficacy [Figure].

Conclusion: High quality evidence suggests Tirzepatide leads to better glycemic control with an acceptable safety profile, along with benefits like weight loss and decreased frequency of administration. Future studies can inform dose optimization and long-term safety.

Disclosure

M. Shamim: None. P. Dwivedi: None. P. Aggarwal: None. R. Dwivedi: None. A. Anil: None. A. Saravanan: None. K. Tiwari: None. R.P. Dodiya: None. I. Yadav: None. S. Sukhija: None. S. Varthya: None. R. Shukla: None. S. Singh: None. K. Singh: None.
803-P: How Effective Is Weight Loss by Oral Semaglutide on Glycemic Control in a Real-World Setting?
Authors: KESAVADEV JOTHYDEV , SHANKAR ARUN , JOSHI SHASHANK R. , ASHIK ASHA , YASMIN SHAHANA , BASANTH ANJANA , RAJ K SOURAV , JOTHYDEV SUNITHA
Published: June 2024

While oral semaglutide is not approved for weight reduction, its injectable form shares which similar pharmacological properties has received FDA approval for the management of obesity. The clinical development program for oral semaglutide has shown potential benefits in body weight reduction in addition to a plethora of benefits. This real-world longitudinal study from a comprehensive diabetes centre in Kerala, India assessed the effect of weight loss on HbA1c levels in T2D using Oral Semaglutide, with follow-up data from March 2022 to July 2023 in 196 subjects. Subjects were divided into three groups based on weight loss: 0-5%, 5-10%, and over 10%. Analysis was conducted using R version 4.3.1, with a significance level set at 5%. In the cohort with a weight reduction of 0 to 5%, there was a significant HbA1c reduction of 1.13% (95% CI = 0.13 to 2.14, p = 0.032). For those who lost 5 to 10% of their weight, HbA1c decreased by 1.3% (95% CI = 0.32 to 2.28, p = 0.015). The most substantial HbA1c reduction, 1.98% (95% CI = 1.11 to 2.85, p = 0.002), was observed in the group that lost more than 10% of their weight. (Figure) This study demonstrates that oral Semaglutide effectively reduces HbA1c levels in T2DM patients, particularly in those with significant weight loss. These findings highlight its potential dual benefit in glycemic control and weight management in T2DM therapy.

Disclosure

J. Kesavadev: None. A. Shankar: None. S.R. Joshi: Consultant; Twin Health, Marico, Franco Indian, Zydus Cadila, Glenmark Pharmaceuticals. Other Relationship; Novo Nordisk, Sanofi, MSD, Abbott Nutrition, Abbott, Biocon, Alkem, USV Private Limited, Boehringer-Ingelheim. A. Ashik: None. S. Yasmin: None. A. Basanth: None. S. Raj K: None. S. Jothydev: None.
827-P: Effectiveness and Safety of Human Insulin Treatment in Elderly Patients with Type 2 Diabetes
Authors: DZIDA GRZEGORZ J. , PASTERCZYK-BIELSKA KATARZYNA , MASIEREK MALGORZATA
Published: June 2024

Due to the progressive nature of type 2 diabetes many older people require insulin therapy. In this age group the achievement of individualized therapy goals should also include maintaining good quality of life. Avoiding hypoglycaemia is the priority. The aim of the study was to determine the distinctiveness of insulin therapy in patients aged 75 year and older when compared to those aged 65-74. The study included 1,914 T2DM patients 65 years of age and older divided into two age groups (group 1, age 65-74 and group 2, age ≥ 75 years ). The observation lasted 3 months between two visits. The analysis is part of a multicentre observational study involving 4,386 people with T2DM treated with human insulin (Gensulin). With adjustment of basal insulin dose significant reduction in A1c was achieved in both study groups. (from 8.5% to 7.8% in the group 1, and from 8.4% to 7.7% in group 2). Achievement A1C target <7% in group 1 increased from 6.3% to 19.3% while target A1c ≤ 8% from 28,0% to 34.0%. In group 2 from 6% to 17,0% and from 56,9% to 81,2% consecutively. A total of 98.2% of patients in group 2 achieved their target A1c. The median daily final insulin dose was 36U in both groups. No severe hypoglycaemia episodes occured. The lack of hypoglycaemia was declared by 83.7% and 82.1% in group 1 and group 2 respectively. Improvement in compliance with recommendations in both age groups was observed, as well as increased satisfaction with the treatment used. There were no significant differences in insulin therapy between patients aged 65-74 years and ≥ 75 years. The optimalization of insulin therapy in elderly patients helps to achieve the target A1c and age over 75 years is not a limiting factor in insulin treatment.

Disclosure

G.J. Dzida: None. K. Pasterczyk-Bielska: None. M. Masierek: Employee; BIOTON.
832-P: Preferences of People with Type 2 Diabetes for Features of Weekly Insulin
Authors: GELSEY FELICIA , PEREZ-NIEVES MAGALY , VASS CAROLINE M. , LING POON JIAT , SCHAPIRO DAVID , PIERCE ANNA , MANSFIELD CAROL
Published: June 2024

Introduction & Objective: For people with type 2 diabetes (PwT2D), daily insulin regimens can be burdensome, difficult to adhere to, and a key barrier to initiating insulin therapy. Despite developments in once-weekly basal insulins, little is known about PwT2D preferences for administration frequency or its importance relative to other insulin features.

Methods: An online discrete choice experiment survey was administered to adults with T2D in the United States. Each respondent completed 8 questions offering a choice between experimentally designed pairs of hypothetical, long-acting insulins that varied by 6 attributes: reduction in A1c level after 6 months, daily time in range, number of serious low blood sugar events, number of nighttime low blood sugar events, weight change over 6 months, and administration frequency. A fixed choice question directly elicited preferences for flexible weekly over daily insulin, holding all other attributes equal. Data were analyzed with random-parameter logits.

Results: A total of 466 people (mean: age = 57; A1c = 7.5%; 59% female) completed the survey. They were on a basal/bolus (33.3%), basal-only (34.3%), or insulin-naïve (32.4%) regimen. Relative to other attributes, people placed most importance on avoiding a 10-pound weight change, followed by the largest changes in the number of serious and nighttime low blood sugar events and achieving the longest time in range. There was significant heterogeneity in preference: insulin-naïve respondents strongly preferred weekly administration, whether on the same day each week or a flexible weekly schedule, over daily (p < 0.05). In the fixed-choice question, most (67.6%) preferred flexible weekly over daily dosing.

Conclusion: Overall, the most important attributes were weight change due to insulin and number of serious hypoglycemic events. PwT2D preferred weekly over daily basal insulin when all other treatment attributes were equal. The dosing flexibility could be crucial for the insulin naïve.

Disclosure

F. Gelsey: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. M. Perez-Nieves: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. C.M. Vass: Other Relationship; Eli Lilly and Company. Consultant; National Institute for Health and Care Excellence (NICE). J. Poon: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. D. Schapiro: Employee; Eli Lilly and Company. A. Pierce: None. C. Mansfield: None.
843-P: Multinational Analysis of Factors Associated with Missed Bolus Insulin Injections Using Smart Pen Data
Authors: JAVIER AMPUDIA BLASCO FRANCISCO , JENSEN MAIKA L. , KAAS ANNE , KNUDSEN NIKOLINE N. , NISHIMURA RIMEI
Published: June 2024

Introduction & Objective: Missing doses in people living with diabetes (PLWD) who use multiple daily insulin injections may lead to inadequate glycemic control. This real-world study assessed the probability of and influencing factors for missed bolus insulin injections in PLWD.

Methods: Data from 21 countries were collected from 22 964 adults with T1D or T2D using CGM and a smart pen (NovoPen 6 or NovoPen Echo Plus) to deliver bolus insulin (2 559 118 CGM and injection days [111 days/adult]). The daily probability of missing ≥ 1 bolus dose (no bolus dose within −15 to +60 mins from meal onset detected by the GRID algorithm) was estimated by a generalized linear mixed model based on logistic regression. Data upload frequency (pen to app) was used as a proxy for smart pen engagement.

Results: The mean probability of having a day with ≥ 1 missed bolus dose was 44.5% (95% CI: 44.1-45.0%), which decreased with increasing age (Figure A) and smart pen data upload frequency (not shown). The probability of having a day with ≥ 1 missed bolus dose was highest on Fridays and Saturdays (Figure B). On any given day, the probability of missing a bolus dose at breakfast, lunch, dinner or snack was 7.5%, 12.2%, 11.1% and 19.4%, respectively.

Conclusion: Bolus insulin adherence increased with age and smart pen engagement and decreased on weekends. Smart insulin pen data can provide novel insights into individuals’ real-world injection behaviors.

Disclosure

F. Ampudia Blasco: Advisory Panel; Novo Nordisk, Sanofi. Speaker's Bureau; Lilly Diabetes. Advisory Panel; Roche Diagnostics, Bayer Inc. M.L. Jensen: Employee; Novo Nordisk. A. Kaas: Employee; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S. N.N. Knudsen: Employee; Novo Nordisk. Stock/Shareholder; Novo Nordisk. R. Nishimura: Speaker's Bureau; Abbott. Advisory Panel; Abbott Japan Co., Ltd. Speaker's Bureau; Boehringer-Ingelheim, Mitsubishi Tanabe Pharma Corporation, Kowa Company, Ltd., Medtronic, Sanofi, Taiho Pharmaceutical Co. Ltd., Sumitomo Dainippon Pharma Co., Ltd., Teijin Pharma Limited, Eli Lilly and Company, Novo Nordisk A/S. Consultant; Terumo Corporation.

Funding

Novo Nordisk A/S
846-P: ALP001E, a Novel Glucagon Receptor Antagonist (GRA), Improves Insulin Resistance, Glycemic Control, and ß-Cell Function in Type 2 Diabetes (T2D)
Authors: CHUNG CHENG-HO , TSENG SHI-LIANG , CHAN PO-CHAO , CASTRO GABRIEL , CHEN YEN-FU , CHEN HSU CHIA , ZEMEL MICHAEL B.
Published: June 2024

Introduction: T2D is characterized by fasting hyperglucagonemia and inappropriate meal suppression of glucagon, resulting in increased endogenous glucose production. While GRA is an attractive T2D target, previous programs have been discontinued due to nonclinical evidence of α-cell hyperplasia and increased blood pressure, LDL, and transaminases in clinical trials. ALP001E is a novel oral GRA with no evidence of these effects in extensive animal testing. ALP001E was well-tolerated in single- and multiple-dose clinical trials, with no significant changes in blood pressure, LDL, or liver enzymes.

Objective: The objective of this trial was to assess pharmacodynamic effects of ALP001E in individuals with T2D.

Methods: A placebo-controlled, double-blind, randomized controlled trial was conducted in 20 T2D patients administered 20, 40, or 80 mg ALP001E or placebo twice daily for 14 days.

Results: Fasting glucose dose-dependently decreased 17-24% by day 2 (-1.50, -1.95, and -2.40 mmol/L for 20, 40, and 80 mg doses, p<0.02) and remained suppressed throughout treatment; there was no significant change in the placebo group. Seven-point glucose dose-responsively decreased at all 7 points from baseline to day 14 for the ALP001E groups but not for placebo; the 80 mg dose group exhibited a 3.1 mmol/L (31.3%) decrease over all 7 points (p<0.05). ALP001E treatment reduced HbA1c by ~5 mmol/L (~10%) across dose groups (p<0.05). Insulin resistance (HOMA2-IR) decreased by 39% vs. placebo overall (p=0.017), with corresponding decreases in fasting insulin, while β-cell function (HOMA2-β) exhibited a marked dose-dependent increase (163% at the 80 mg dose, p<0.05). Overall, ALP001E was safe and well-tolerated at all doses; all reported TEAEs were mild, with no dose discontinuation or dose-changes secondary to AEs.

Conclusion: ALP001E has robust therapeutic potential for improving insulin resistance and glycemic control in patients with T2D.

Disclosure

C. Chung: Board Member; Alphala Group Inc. Caymen. S. Tseng: None. P. Chan: Employee; CMC Magnetics Corporation. G. Castro: None. Y. Chen: Employee; CMC Magnetics Corporation. C. Hsu: None. M.B. Zemel: Consultant; Enterin, TIXiMed, Glyscend Inc. Board Member; NuSirt. Consultant; Levicure, Seraxis, Aerami, Zealand Pharma A/S, Adipopharm.
848-P: Comparing Generative AI to Human Responses for Personalized Diabetes Drug Selection
Authors: FLORY JAMES , ANCKER JESSICA , KUPERMAN GILAD , VICKERS ANDREW , KIM SCOTT Y. , PETROV ALEKSANDR
Published: June 2024

Introduction and Objective: Generative artificial intelligence (AI) offers great promise for clinical decision support (CDS). When there is a single right answer to a clinical question, assessing whether a generative AI is appropriate for CDS may be simple: does it give the correct answer often enough? When there is not a clear best answer, assessing AI performance is more complex.

Methods: This study compares endocrinologist and AI (Chat GPT-4) responses to clinical vignettes in which the respondent was asked to choose an initial medication for a patient with type 2 diabetes. Each vignette included patient characteristics such as lab values, demographics, and comorbidities. Use versus non-use of metformin was the primary outcome. Univariable analysis was used to explore how other patient characteristics influenced willingness to use metformin.

Results: Both endocrinologists (n=30) and AI were unlikely to recommend metformin in severely impaired kidney function (Figure 1A). Patient characteristics affected human and AI responses in similar ways (Figure 1B). Human respondents were slightly less likely to use metformin in patients with history of gastrointestinal symptoms, while the AI never used metformin in those circumstances.

Conclusion: When multiple treatment options were reasonable, AI responses were similar to human responses in quality and in how treatment decisions were personalized.

Disclosure

J. Flory: None. J. Ancker: Other Relationship; Ambry Genetics. G. Kuperman: None. A. Vickers: None. S.Y. Kim: None. A. Petrov: None.

Funding

Patient Centered Outcomes Research Institute (ME-2022C1-26378)
853-P: Efficacy and Safety of HD-6277, a Novel GPR40 Agonist, in Patients with Type 2 Diabetes—A Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multicenter Phase 2 Trial
Authors: LEE YONG-HO , MIN KYUNGWAN , HWA HONG JUN , LIM SOO , YU JAEMYUNG , CHUNG CHOON H. , SUNG MOON JUN , CHUL WON JONG , WOO AHN CHUL , LEE JIE-EUN , NYUN KIM TAE , LEE BYUNG-WAN
Published: June 2024

Objective: To assess the efficacy and safety of HD-6277, the first candidate of GPR40 in a new oral antidiabetic agent, in Adult Patients With Inadequate Control of Type 2 Diabetes Mellitus (T2DM)

Research Design & Methods: A double-blind, randomized, placebo-controlled phase 2 trial recruited 112 participants aged ≥ 20 years with T2DM with HbA1c between 7.0% and 10.0% while on diet and exercise alone for at least 8 weeks prior to screening. Parallel-group, randomized trial of HD-6277 50mg and 100mg group versus placebo were assigned for 12 weeks. The primary outcome was change in HbA1c at week 12 from baseline. Secondary outcomes included proportion of patients achieving HbA1c less than 7.0%, change in fasting plasma glucose(FPG), Changes in blood levels of post-meal glucose, insulin, glycoalbumin(GA), and C-peptide at week 12. In addition, changes in fasting lipid parameters, weight, GA/HbA1c ratio, HOMA (Homeostasis Model Assessment) β, and CD 36 were evaluated as exploratory endpoints.

Results: At week 12, compared to the placebo group, HD-6277 50mg and 100mg resulted in a statistically significant reduction of HbA1c levels by -0.73(95% CI -1.11, -0.35), p=0.0002 and -0.85 (95% CI -1.21, -0.50), P<0.0001, respectively. No significant increase in treatment-related adverse events was observed for HD-6277. Furthermore, significant improvements in FPG and GA levels were confirmed in the HD-6277 administration group compared to the placebo.

Conclusion: HD-6277 50mg and 100 mg improved glycaemic control in patients with T2DM inadequately controlled with diet and exercise, as shown by significant changes in HbA1c and FPG. The treatment with HD-6277 appeared to be safe and well tolerated. A GPR40 agonist represents a potential new treatment option for T2DM.

Disclosure

Y. Lee: None. K. Min: None. J. Hong: None. S. Lim: None. J. Yu: None. C.H. Chung: None. J. Moon: None. J. Won: None. C. Ahn: None. J. Lee: None. T. Kim: None. B. Lee: Research Support; Hyundai Pharm.

Funding

This study was sponsored by Hyundai Pharmaceutical Co., Ltd. (ClinicalTrials.gov registration number: NCT05666128).
855-P: GLY-200 (Oral Pharmacologic Duodenal Exclusion Drug) Reduces Glucose and Bodyweight in Patients with Type 2 Diabetes
Authors: FINEMAN MARK , COLBERT KEVIN , PETERSEN JOHN S. , JOZEFIAK THOMAS H. , NIMGAONKAR ASHISH , BRYANT CHRISTINE
Published: June 2024

Background: GLY-200 is an investigational oral non-absorbed polymer drug designed to bind to and enhance the barrier function of gastrointestinal mucus as a non-invasive alternative to metabolic surgery and duodenal exclusion devices. In healthy volunteers, GLY-200 lowered glucose and increased GLP-1, PYY, and bile acids, indicating pharmacologic effects in the proximal small intestine. This study evaluated the safety, tolerability, and pharmacodynamic effects of GLY-200 in patients with type 2 diabetes (T2D).

Methods: In this randomized, double-blind, placebo (PBO)-controlled study, 51 patients with T2D [BMI 31.3 ± 4.2 kg/m2, baseline (BL) HbA1c 7.12 ± 0.57%] received 14 days of 0.5, 1.0, or 2.0 g GLY-200 or PBO, BID. Assessments included safety/tolerability, food intake, appetite, body weight (BW), glucose profiles after a standardized meal, and CGM.

Results: GLY-200 appeared safe and well-tolerated with most AEs being GI-related. Glucose was reduced on Day 1 in the 2.0 g GLY-200 group and reduced over time with lower doses. Day 14 iAUC was ↓27% (p=0.11), ↓29% (p=0.13), and ↓44% (p=0.01) in the 0.5, 1.0, and 2.0 g GLY-200 groups, respectively, vs PBO. At Day 14, the mean change from BL in fasting serum glucose was ‑16.1, -10.7, -16.1 mg/dL for the 0.5, 1.0, and 2.0 g GLY-200 groups, respectively, compared to an increase of 12.1 mg/dL in the PBO group. Decreases from BL in total and LDL cholesterol were also seen at Day 7 and 14 in 1.0 g and 2.0 g GLY-200 groups. Progressive reductions in BW were seen over the 14-day treatment period, with the largest reductions seen with 2.0 g GLY-200 (up to -1.8% change from BL). 2.0 g GLY-200 subjects also reported reduced appetite, increased satiation, and reduced food intake.

Conclusion: GLY-200 treatment resulted in positive effects on fasting and postprandial glucose, lipid profiles, food intake, appetite suppression, and BW consistent with the antidiabetic and anti-obesity effects of other more invasive approaches to duodenal exclusion.

Disclosure

M. Fineman: Employee; Glyscend Inc. K. Colbert: Employee; Glyscend Inc. Consultant; LifeSprout Inc. J.S. Petersen: None. T.H. Jozefiak: Employee; Glyscend Inc. A. Nimgaonkar: None. C. Bryant: Employee; Glyscend Inc.
856-P: Prevention of Type 1 Diabetes with MSC-EV
Authors: GU ANGEL S. , BAG ARUP , HO YINWEI , RAO ANITHA , RODRIGUEZ KEITH , MIAO LYNN N. , RAWSON JEFFREY , HUSSEINY MOHAMED I. , KANDEEL FOUAD R.
Published: June 2024

Objective: Type 1 diabetes (T1D) is an autoimmune disease characterized by immune cell-mediated destruction of beta cells resulting in loss of insulin production and glucose homeostasis. Mesenchymal stem cells (MSCs) are a heterogeneous population of adult stem cells that can be isolated from many tissues including umbilical cords. Extracellular vehicles (EVs) derived from human MSCs have been proposed to have the potential for restoring immune tolerance and to block the immune/inflammatory attack on beta cells. We examined the ability of human MSC-EV to prevent transfer of T1D in mice.

Methods: Adoptive transfer of T1D was performed in 7-week-old female NOD/SCID mice received 10 x 106 splenocytes from 12-week-old female NOD mice, followed 24 hours later with either PBS, 1 x 106 MSCs or 5 x 109 MSC-EVs, two doses each, 7 days apart. Blood glucose was monitored daily, and IPGTT was performed before animal sacrifice. Blood, splenocytes and pancreas were then harvested.

Results: Mice treated with EVs or MSCs showed reduction in the development of diabetes. More germane, EV-treated animals fared best with 75% showing no diabetes at 9 weeks post treatment. IPGTT data showed that mice treated with EVs have less rise in blood glucose and faster restoration towards baseline compared to MSC- and PBS-treated animals. Further, these mice showed less overall glucose variability during the test. The splenocytes from EV-treated mice produced significantly less inflammatory cytokines MIP-2, IL-1α and IL-12 and more anti-inflammatory IL-10 compared to splenocytes from PBS-treated mice. FACS analysis found more regulatory CD4/Foxp3 and CD4/CD25/Foxp3 positive T cells in the circulation of EV-treated mice compared to controls. MSC and EV-treated mice displayed more insulin-positive beta cells compared to PBS-treated animals, but density of these cells were less in the MSC than the EV-treated group.

Conclusion: MSC-EV therapy can prevent development of T1D more effectively than MSCs, presenting a huge opportunity for patients at risk or having established T1D.

Disclosure

A.S. Gu: None. A. Bag: None. Y. Ho: None. A. Rao: None. K. Rodriguez: None. L.N. Miao: None. J. Rawson: None. M.I. Husseiny: None. F.R. Kandeel: Advisory Panel; Vertex Pharmaceuticals Incorporated.
864-P: GLY-200 (Oral Pharmacologic Duodenal Exclusion Drug) Decreases Appetite, Increases Satiation, and Reduces Food Intake in Patients with Type 2 Diabetes
Authors: BRYANT CHRISTINE , NIMGAONKAR ASHISH , FINEMAN MARK
Published: June 2024

Background: GLY-200 is an investigational oral non-absorbed polymeric drug designed to bind to and enhance the barrier function of gastrointestinal mucus as a non-invasive alternative to metabolic surgery and duodenal exclusion devices. In healthy volunteers, GLY-200 lowered glucose and increased GLP-1, PYY, and bile acids, indicating pharmacologic effects of duodenal targeting. This 14-day Ph2 study in patients with type 2 diabetes (T2D) evaluated the safety, tolerability, and pharmacodynamic effects of GLY-200 and showed reduced glucose and progressive body weight loss at the 2.0 g GLY-200 dose.

Methods: Randomized, double-blind, placebo (PBO)-controlled inpatient study with 14 days BID dosing of 2.0 g GLY-200 [N=13, BMI 31.8 ± 4.1 kg/m2, baseline (BL) HbA1c 7.2 ± 0.7%] and PBO (N=12, BMI 31.7 ± 3.2 kg/m2, BL HbA1c 7.2 ± 0.7%). On Day -1, 1, and 13, food intake and appetite VAS were assessed at standardized breakfasts and ad libitum dinners. Categorical food intake (0-25%, 26-50%, 51-75%, 76-100% consumed) was assessed at all other inpatient meals.

Results: GLY-200 appeared safe and well-tolerated with most AEs being GI-related. With 2.0 g GLY-200, a greater overall appetite suppression (OAS) score was seen immediately post-meal (↑35.9%, p=0.004) and 60 min after the standardized breakfast (↑28.7, p=0.02) vs PBO. Before the ad libitum dinner, the OAS score was ↑28% (p=0.004) in 2.0 g GLY-200 subjects vs PBO. When allowed to eat as much as desired, 2.0 g GLY-200 subjects had significantly lower food intake (↓17.0%, p=0.026). During non-standardized inpatient meals, an average of 22.1%, 19.5%, and 28% of 2.0 g GLY-200 subjects consumed ≤75% of breakfast, lunch, and dinner, respectively, vs 0%, 4.8% and 6.8% of PBO subjects.

Conclusion: Increased satiation/satiety, decreased feeling of hunger, and reduced food intake, in part, explains the body weight loss observed with 2.0 g GLY-200 treatment, consistent with the intended mechanism of the drug.

Disclosure

C. Bryant: Employee; Glyscend Inc. A. Nimgaonkar: None. M. Fineman: Employee; Glyscend Inc.
867-P: Cardiovascular Outcomes in Patients Initiating a Second Diabetes Medication after Metformin—The BESTMED Study
Authors: TURCHIN ALEXANDER , PETITO LUCIA , HEGERMILLER EMMA , CARNAHAN RYAN M. , KITZMAN HEATHER , CECILIA LANSANG M. , MCDONNELL MARIE E. , NAIR VINIT , PRIEST ELISA L. , WILLEY VINCENT , GOEL SATYENDER , KAUL ALAN F. , HERNAN MIGUEL
Published: June 2024

Introduction: In patients with T2D at high cardiovascular (CV) risk, several classes of medications have been found to reduce incidence of CV events. However, long-term CV outcomes of T2D medications in lower risk patients are unknown.

Methods: We conducted a causal inference study by emulating a target trial using observational data from 12 health systems and insurance plans across the US. Eligible individuals were patients with T2D and hyperglycemia (HbA1c 7.0-11.0% or equivalent glucose levels) at moderate CV risk (no CV disease) on metformin monotherapy who initiated a second T2D medication between 01/01/13 and 09/01/21, with eGFR ≥ 45 ml/min/1.73m2 and with no contraindications to study medications. We compared patients initiating one of the following medication classes: DPP4s, GLP1s, SGLT2s and sulfonylureas (SUs). In each treatment arm we estimated the 5-year risk of a composite outcome (MI, ischemic CVA, HF hospitalization or CV death) after adjustment for demographics, comorbidities and laboratory values at baseline.

Results: We studied 55,441 patients followed for a median of 32 (IQR 18-54) months, with a median age of 60 (IQR 52-68) years and median baseline HbA1c of 7.8% (IQR 7.3-8.6%). Of these, 11,195 patients initiated a DPP4, 6,920 a GLP1, 7,911 an SGLT2 and 29,415 an SU; 40,673 (73.4)% of patients stopped the original study drug class before the end of follow-up after a median of 11 (IQR 3-22) months. A total of 2,566 (4.6%) of patients experienced the primary outcome endpoint. The estimated 5-year risk ratios (95% CI), compared to DPP4s, were 0.93 (0.73 - 1.13) for GLP1s, 0.96 (0.83 - 1.14) for SGLT2s and 1.08 (0.98 - 1.19) for SUs.

Conclusions: Among patients with T2D at moderate CV risk on metformin monotherapy, incidence of CV events was similar among four classes of most commonly used non-insulin T2D medications. Further research is needed to evaluate the risk of non-CV events to help patients and clinicians to make informed decisions on T2D therapy.

Disclosure

A. Turchin: Research Support; Eli Lilly and Company, Novo Nordisk. Consultant; Novo Nordisk, Proteomics International. Research Support; AstraZeneca. L. Petito: Research Support; Omron Healthcare Co., Ltd. E. Hegermiller: None. R.M. Carnahan: None. H. Kitzman: Advisory Panel; Novo Nordisk. M. Lansang: Research Support; Abbott, Dexcom, Inc. Consultant; Glooko, Inc. Research Support; Xeris Pharmaceuticals, Inc. M.E. McDonnell: None. V. Nair: None. E.L. Priest: Research Support; Boehringer-Ingelheim, AstraZeneca, Owkin. V. Willey: Other Relationship; Carelon Research. S. Goel: None. A.F. Kaul: None. M. Hernan: Consultant; ProPublica, Cytel. Other Relationship; ADIA Lab, Flatiron, Foundation Medicine.

Funding

PCORI (DB-2020C2-20308)
868-P: Efficacy and Safety of Crisugabalin with Acetyl-Levo-Carnitine in Chinese Patients with Diabetic Peripheral Neuropathic Pain—A Multicentre, Randomized, Open-Label, Positive-Controlled, Parallel-Group, Phase 2 Trial
Authors: JIANG HONGWEI , FU LIUJUN , XU NA , SHANG JUNJIE , YANG QIUWEI
Published: June 2024

Background: Crisugabalin (HSK16149) was found to be a novel, potent treatment option for patients with diabetic peripheral neuropathic pain (DPNP); However, efficacy and safety data specifically for Chinese individuals were limited to several researches, and there was no comparative evidence on whether drugs should be combined. This study aimed to assess the efficacy and safety of Crisugabalin combined with acetyl-levo-carnitine (ALC) and lipoic acid (LA) combined with ALC for treatment of DPNP in China.

Methods: Adults (≥18 years) with DPNP, 40 mm≤VAS≤90 mm at screening were eligible for study participation. Subjects were randomized (1:1) to Crisugabalin (20mg, bid) combined with ALC (0.5g, tid), and LA (0.6g, qd, iv in 1 week, po in 2-12 week) combined with ALC (0.5g, tid) for 12 weeks. The primary endpoint was the change in average daily pain score (ADPS) from baseline to week 12. Key safety endpoints were the types and incidence of treatment-emergent adverse events (TEAEs) monitored throughout the trial.

Results: A total of 134 patients were randomized to receive Crisugabalin with ALC (n=68) or LA with ALC (n=65). Here we report initial results from interim analysis of the trial. At week 12, the mean ADPS change from baseline was -2.1 and -4.1 for LA (n=42) and Crisugabalin (n=44) group, showing statistical significance for Crisugabalin versus LA group (P<0.0001). Most TEAEs in two groups were mild to moderate, and no investigational drugs-related TEAEs CTCAE≥3 happened throughout the study. The most frequent TEAEs in Crisugabalin group were dizziness (9/68, 13.2%) and somnolence (6/68, 8.8%).

Conclusion: These preliminary data demonstrated that Crisugabalin with ALC was superiority to LA with ALC in relieving pain and well tolerated in Chinese patients with DPNP.

Disclosure

H. Jiang: None. L. Fu: None. N. Xu: None. J. Shang: None. Q. Yang: None.
87-OR: A PKA to mTORC1 Signaling Axis Controls Metabolic Homeostasis via Phosphorylation of Raptor
Authors: SHI FUBIAO , LIU DIANXIN , ZHANG WEI , PATEL HARI U. , SHRESTHA SHRISTI , CARTAILLER JP , LI JIAN-LIANG , COLLINS SHEILA
Published: June 2024

As critical mediators of cellular signaling, the second messenger cAMP and its associated protein kinase A (PKA) can function by regulating the activity of the mechanistic target of rapamycin complex 1 (mTORC1). However, the signaling mechanism and physiological significance underpinning this regulation have not been fully defined. Using the adipocyte as a model, we show that PKA phosphorylation of Ser791 in Raptor, the defining component of mTORC1, is required for mTORC1 activation by β3-adrenergic receptor (β3AR) stimulation. Mice with a phospho-resistant Raptor Ser791 to Ala (S791A) mutation specifically in adipocytes (adS791A) show impaired adipose browning after β3AR agonist CL-316,243 (CL) treatment. They develop adipose inflammation, fatty liver, and insulin resistance on high-fat diets. In follow-up hyperinsulinemic-euglycemic clamp studies, they manifest reduced glucose infusion rates, increased hepatic glucose production, and decreased skeletal muscle glucose uptake. Mechanistically, the adipocyte S791A mutation blunts CL-induced mTORC1 activity and leads to degradation of the PPARγ protein. In addition to PPARγ, the level of β3AR protein is also reduced in Raptor adS791A mice. We have identified PPARγ binding sites along with a known critical C/EBPα site in the β3AR promoter, suggesting PPARγ, with C/EBPα, could be a transcriptional regulator of β3AR expression. In contrast, expression of a constitutively active phospho-mimetic Raptor Ser791 to Asp (S791D) mutant in brown adipocytes results in transcriptomic changes indicative of greater PPARγ activity and enhanced adipocyte thermogenesis gene program. These data indicate that Raptor S791 phosphorylation might act through a PPARγ-dependent mechanism to control adipose tissue function. Taken together, our study reveals the functional consequence for the PKA phosphorylation of Raptor in adipocyte metabolism and presents a novel mechanism by which the cAMP-PKA pathway controls the mTORC1 signaling network.

Disclosure

F. Shi: None. D. Liu: None. W. Zhang: None. H.U. Patel: None. S. Shrestha: None. J. Cartailler: None. J. Li: None. S. Collins: None.

Funding

National Institutes of Health (R01DK116625 to SC), American Heart Association (23CDA1048341 to FS)
872-P: Tolerization Therapy for Treating Type 1 Diabetes Mellitus
Authors: DE HAAN PETER
Published: June 2024

Introduction & Objective: Type 1 Diabetes Mellitus (T1DM) is an autoimmune disease in which T lymphocytes infiltrate pancreatic Langerhans islets and destroy insulin-producing β-cells. Amarna has developed a viral gene delivery vector platform named SVec that based on its safety, non-immunogenicity and tolerogenic properties may be effective in inducing/restoring immune tolerance to the primary self-antigens of autoimmune diseases to thereby halt or revert autoimmune disease progression. We wanted to test the feasibility of SVec for the development of an effective tolerization therapy for T1DM.

Methods: Two SVec vectors encoding the primary self-antigens of the disease e.g. proinsulin (SVPI) and preproinsulin (SVPPI) were generated and vector particles produced in our SuperVero packaging cells. To obtain hepatic transgene expression groups of ten female non obese diabetic (NOD) mice were administered intravenously with SVPI or SVPPI particles six weeks after birth at a dose of 2.5x107 IU/kg body weight and glycemia was monitored up to 30 weeks after birth.

Results: Ninety percent of the untreated NOD mice developed hyperglycemia within this time span, whereas only forty percent of the SVPI-treated mice became hyperglycemic. SVPPI did not protect female NOD mice from developing T1DM. Histological inspection of the pancreases revealed that the tolerized NOD mice with SVPI had healthy islets and islets partially infiltrated with T lymphocytes. On the contrary, the pancreases of untreated mice or those injected with SVPPI were completely or partially infiltrated with T lymphocytes. Conclusion: The induction of immune tolerance to proinsulin in the liver stops the autoimmune destruction of pancreatic β-cells and hence disease progression in mice that were on their way to develop T1DM. SVec is therefore highly promising for inducing antigen-specific immune tolerance and thus for developing effective and safe tolerization therapies for patients with an autoimmune disease including T1DM.

Disclosure

P. de Haan: None.
876-P: Imeglimin, a Novel, First-in-Class Glimin Helps in Maintaining ß-Cell Function in Patients with Recent-Onset Latent Autoimmune Diabetes in Adults—A Nine-Month Prospective Study
Authors: GADVE SHARVIL S. , GADVE SNEHA S. , GADVE SHRIYA , CHAVANDA KETKI S. , HANAMSHETTI SATISH
Published: June 2024

Objective: Imeglimin is being used in T2DM. The effect of imeglimin on β-cell function in patients with latent autoimmune diabetes in adults (LADA) is not known, however, based on its mechanism of action, imeglimin could be expected to preserve pancreatic β-cell function in LADA patients. The objective of the study was to evaluate the effects of the imeglimin on β-cell function in patients with recent-onset LADA.

Research Design & Methods: This was an open-label, randomized-controlled trial conducted in a specialized diabetes care unit in India. Thirty Six recently diagnosed LADA patients were randomized to receive insulin therapy with 1000 mg twice a day imeglimin (n = 18) or without imeglimin (n = 18) for 9 months. Fasting and 2-hour postprandial blood samples were obtained at baseline and after 3, 6, and 9 months of treatment to determine blood glucose, glycosylated hemoglobin, and C-peptide levels.

Results: There were no significant differences in glucose and glycosylated hemoglobin levels between the two groups during 9 months of follow-up. At 9 months, fasting C-peptide, 2-hour postprandial C-peptide, and increment in C-peptide (delta CP) levels were not different in Insulin plus imeglimin group (P > .05) compared with baseline, whereas in Insulin without imeglimin group the levels of fasting C-peptide, 2-hour postprandial C-peptide, and increment in C-peptide (delta CP) levels were significantly decreased compared with baseline (P < .05). Levels of 2-hour postprandial C-peptide were higher in Insulin plus imeglimin group than Insulin without imeglimin group at 9 months (P < .05).

Conclusions: Imeglimin helps in maintaining β-cell function in patients with recent-onset Latent Autoimmune Diabetes in Adults when given with insulin when compared to insulin given alone.

Disclosure

S.S. Gadve: None. S.S. Gadve: None. S. Gadve: None. K.S. Chavanda: None. S. Hanamshetti: None.
884-P: Duodenal Electroporation and Semaglutide Effectively Eliminate Need for Insulin in Type 2 Diabetes Patients
Authors: BUSCH CELINE B.E. , MEIRING SUZANNE , VAN BAAR ANNIEKE C.G. , HOLLEMAN FRITS , NIEUWDORP MAX , BERGMAN JACQUES
Published: June 2024

Introduction: Re-Cellularization via Electroporation Therapy (ReCET™) is an endoscopic ablation technique which uses electroporation of cellular membranes to elicit apoptosis of the duodenal mucosa. We aimed to eliminate insulin therapy in T2D patients by combining a single ReCET procedure with a GLP-1 receptor agonist (GLP-1RA).

Methods: First-in-human study with 14 patients with T2D on basal insulin (BMI 24-40kg/m2; HbA1c≤8.0%; C-pep≥0.2nmol/l). All underwent ReCET after which semaglutide was titrated up to 1mg/week. Primary endpoints were feasibility (technical success, procedure time, GLP-1RA tolerance), safety ([S]AE, hypoglycemic events) and efficacy (off insulin at 6 months; HbA1c≤7.5%). Metabolic and glycemic data was collected throughout 24 months follow-up.

Results: ReCET showed 100% technical success rate. Procedure time was 58 min. Max semaglutide dosage was tolerated by 13 patients. No device related SAEs or severe hypoglycemic events were observed. At 6 months 12 patients (86%) were off insulin and remained off insulin at 9, 12 and 18 months (24mo data available Jan 2024). Despite being off insulin, glycemic and metabolic parameters improved significantly (Table 1).

Conclusion: ReCET appears to be safe and, when combined with semaglutide, can effectively eliminate the need for insulin up to 18 months in T2D patients, while improving glycemic control and metabolic health.

Disclosure

C.B.E. Busch: None. S. Meiring: None. A.C.G. van Baar: None. F. Holleman: None. M. Nieuwdorp: Stock/Shareholder; Caelus Health, AMI therapeutics. J. Bergman: Research Support; Fractyl Health, Inc. Consultant; Fractyl Health, Inc. Research Support; Endogenex. Consultant; Endogenex. Research Support; Digma. Consultant; Digma. Research Support; Aqua Medical. Consultant; Aqua Medical.

Funding

An unrestrided research grant by Endogenex.
9-PUB: Water Consumption Evaluation during a Short Weight Loss Program
Authors: CONSTANTIN CIPRIAN , CONSTANTIN GEORGIANA , LULIA STAICU M. , IJACU ANA M. , DRAGOICEA MIHAI , ZUGRAVU CORINA , GAGIU LAURA G.
Published: June 2024

The aim of this study was to evaluate the water consumption during an interventional program using glucagon like peptide 1 receptor analog (aGLP1) or inhibitors of sodium glucose-cotransporter2 (iSGLT2) medication at type 2 diabetes mellitus (T2DM) patients. This was a retrospective study during the year 2023, using data from multiple centers. We included 45 T2DM patients (23women and 22men), age (mean±standard deviation) 61,12±6,13years, duration of T2DM 5,16±1,41years, BMI=34,4±3,15kg/m2, HbA1c=7,20±0,2%, divided in 3 similar lots (p>0.05). All these groups were matched according to all important characteristics at the beginning. All patients were initially treated with metformin (met) 2g/day. After first evaluation we consider: lot A received iSGLT2 plus met, lot B received aGLP1 plus met and lot C with met. All patients received 10%calories reduction program in normal conditions. Targets were established using ADA23 guidelines. Observational parameters at baseline and after 1 and 3 months included water consumption (WaCo) liter/day, estimation in a 3 day-journal. Initially and in the end were determinate HbA1c and BMI. In our study it seems to be a significant clinical difference during a regular losing weight program considering water consumption (p>0,05). Significant differences were observed comparing lot A vs. lot B and lot A vs. lot C when we kept the different antidiabetic medication used during this program (p<0,05).

Disclosure

C. Constantin: None. G. Constantin: None. S.M. Lulia: None. A.M. Ijacu: None. M. Dragoicea: None. C. Zugravu: None. L.G. Gagiu: None.

Funding

Research Metabolism Center - Romania
906-P: Safety and Efficacy of Polmacoxib for Diabetes-Associated Frozen Shoulder—Prospective Randomized Control Trial
Authors: GAUTAM ASHISH , AGRAWAL PRABHAT K. , PURSNANI NIKHIL , YADAV SHAILENDRA K. , YADAV ALKA
Published: June 2024

Introduction and Objective: Adhesive Capsulitis (AC) or frozen shoulder is a common complication of uncontrolled T2DM having prevalence of 10-39%. Shoulder pain and disability index(SPADI) is visual analogue scale tool to quantify disease severity in AC. Polmacoxib, a novel COX2 inhibitor is indicated for long term analgesia in osteoarthritis without CV side effects. Besides COX2 Inhibition it has high affinity to carbonic anhydrase (CA) enzyme. A preferential binding of Polmacoxib to CA reduces COX2 effects in cardiovascular system where it is present in abundance. Thus, preventing CV side effects. Prolonged effective analgesic, physiotherapy and strict glucose control are main stay treatment of AC. Objective was to study Polmacoxib as safe and effective analgesic in T2DM associated AC.

Methods: Eighty-six participants with T2DM and AC without CV disease were divided into 2 groups (43 cases and 43 comparators) after randomization. SPADI tool used before start of therapy and then weekly till 6 weeks in both groups. Increase in wight 5% and heart rate 10% above baseline, new onset pedal edema &/or right hypochondrial tenderness, easy fatigability &/or unexplained cough were measured signs of fluid accumulation and incipient CHF and considered early study termination. Standard diabetes care and physiotherapy given to both groups. Cases were given oral Polmacoxib 2 mg/day and Comparators oral tramadol sos for pain. A >80% SPADI score reduction was considered cut-off for effective analgesia.

Results: one case lost follow up, so excluded. Thirty six out of 42 cases whereas 28 out of 43 comparators showed >80% reduction in SPADI score at 2 wks. which was maintained till 6 wks. The proportion of participants who reported reduction in pain and disability above cutoff differ by use of Polmacoxib, X2 (1, N = 85) = 4.84, p < .05. No participant showed any sign of CHF during study.

Conclusion: Polmacoxib was an effective and safe analgesic for prolong use in adhesive capsulitis due to T2DM

Disclosure

A. Gautam: None. P.K. Agrawal: None. N. Pursnani: None. S.K. Yadav: None. A. Yadav: None.