bluuebunny/crossref_metadata_2025_split huggingface dataset:
1170-P: Alleviation Effects of a Traditional Chinese Medicine on Diabetes in Rats Linked to Modulation of the Gut Microbiome
Authors: TIAN JIAXING , LI MIN , TONG XIAOLIN 
Published: June 2019

Introduction: Gegen Qinlian Decoction (GQD) is a Chinese herbal medicine that has been reported to significantly decrease blood glucose levels, which is suggested to be related to interactions with the gut microbiota. However, the protective effect of GQD on intestinal barrier function with regard to its influence on the gut microbiota has not been explored to date. In this study, we investigated the role of the gut microbiota in mediating the hypoglycemic mechanism of GQD in type 2 diabetes mellitus (T2DM) rats.
Methods: The T2DM rats were randomly allocated to receive GQD, metformin (Met), or distilled water for 12 consecutive weeks, and changes in metabolic parameters, intestinal barrier function, and inflammation were investigated. Gut microbiota were analyzed using 16S rRNA sequencing from fecal samples, and statistical analyses were performed to correlate microbiota composition with phenotypes of the T2DM rats.
Results: Both GQD and Met administration decreased the levels of blood glucose and inflammatory factors, and increased the levels of tight junction proteins. However, GQD had a greater protective effect on islet function, restoring intestinal permeability, and inhibiting inflammation than Met, as evidenced by improvements in the levels of occludin and claudin-1 in the colon, and the expressions of serum inflammatory factors. In addition, GQD regulated the structure of the gut microbiota by increasing the proportions of short-chain fatty acids-producing and anti-inflammatory bacteria, and decreasing the proportions of conditioned pathogenic bacteria associated with the diabetic phenotype.
Conclusion: GQD could ameliorate hyperglycemia and protect islet function by regulating the structure of the gut microbiota, thereby restoring intestinal permeability and inhibiting inflammation in T2DM rats. Our study thus suggests that the hypoglycemic mechanism of GQD is mediated by its modulation of the gut microbiota.

Disclosure
J. Tian: None. M. Li: None. X. Tong: None.

Funding
National Natural Science Foundation of China (81430097); China Association for Science and Technology (CACM-2017-QNRC1-02)
1171-P: Effect of Genetic Testing for Weight Loss on Adult Patients
Authors: JAMES KATHY S. 
Published: June 2019

Background: It is well-known in obesity research and clinical practice that there are differing responses to dietary interventions.
Genetic evaluation based on metabolic genotypes has been found helpful in understanding which dietary and activity recommendations are a best fit for weight management.
Purpose: This study provided information on practicality, acceptability, and effectiveness of incorporating Genetic Influenced to Personalize Dietary and Exercise Plans (GIPDEP) in clinical practice. We assessed the efficacy of personalized weight loss recommendations based on genetic information compared to conventional care.
Sample: Patients (N=92; on average 47 years of age [range: 22 to 71]; 78 females; 3 with normal weight, 27 overweight, 62 obese) from a community-based weight loss clinic were randomly assigned to the treatment (51 received genotype test screening) and the control (40 received conventional care) groups stratified by age, gender, initial BMI, and score in the Weight Efficacy Lifestyle (WEL) scale. Measures: The Weight Efficacy Lifestyle questionnaire ([WEL] was used to assess confidence in ability to lose weight. Patients were assessed twice (beginning, 4-month follow-up).
Results: At four months, both groups showed comparable decrease in BMI (treatment: Δ(ΒΜΙ)=-0.87±2.06; control: Δ(ΒΜΙ)=-0.81±1.54; Wilcoxon Rank Sums test, p=0.908). Multiple regression was used to assess the effect of treatment on Δ(ΒΜΙ) adjusting for age, gender, exercise, health issues limiting exercise, and daily sleep. In all models, treatment was not a statistically significant predictor of Δ(ΒΜΙ) (all p &gt; 0.50).
Summary: Results do not provide evidence that weight loss recommendations based on genetic screening are more advantageous than conventional recommendations. The non-finding may be explained if we consider that weight loss is associated with a number of factors, i.e., self-efficacy, support, etc. The advantage of optimal recommendations may be masked by these other factors.

Disclosure
K.S. James: None.

Funding
Allen Foundation Inc.
1174-P: Improvements of Insulin and Leptin Sensitivity for Type 2 Diabetes and Obesity by Cyclo-(His-Pro) plus Zinc Treatment
Authors: SONG MOON K. 
Published: June 2019

Cyclo (his-pro) plus zinc (Cyclo-Z) treatment improved insulin and leptin sensitivity without any known side effects in animal studies. We now report the results of a randomized, double-blind, placebo-controlled multicenter FDA approved phase 2a clinical trial with obese diabetic subjects. A total of 64 subjects with hemoglobin A1c (HbA1c) levels between 7.5 and 10 and body mass index (BMI) above 30 were recruited in 4 different treatment groups: A:3 mg CHP, B:9 mg CHP; or C:15 mg CHP plus 23 mg zinc in all three treated groups; D: placebo to take one capsule by every subject at bedtime daily. HbA1c, OGTT, plasma insulin and leptin levels, were determined every 4 weeks while body weight, BMI and side effects were determined every 2 weeks. During the 12-week study period, HbA1c levels changed from baseline at 12 weeks as A: -0.247 ± 0.198 %; B: -0.233± 0.282%; C: -0.586± 0.250%; D: 0.05 ± 0.248%. p=0.0824 C vs. D. Body weight changed. A:0.479 ± 1.032 kg; B: 0.738 ± 0.784 kg ; C: -0.962 ± 0.6 29 kg ; D: 1.456 ± 0.772 kg. P=0.0249 C vs. D. TAFGC (OGTT) changed. A: -2.675 ± 10.336 mg/dL/hour; B: -2.399 ± 8.197 mg/dL/hour; C: -14.895 ±5.751mg dL/hour; D:0.8475 ± 13.515 mg/dL/hour. p=0.039 C vs. D. BMI changed. A: -0.089± 0.358 kg/m2; B: 0.008± 0.186 kg/m2; C: -0.291 ± 0.186 kg/m2; D:1.023 ± 0.493 kg/m2. P=0.049 C vs. D. Plasma insulin levels changed. A:4.269 ± 8.115 µU/mL; B: 2.787 ± 2.566 µU/mL; C: -5.0 ± 10.795 µU/mL; D: 29.787± 28.513 µU/mL. P=0.0296 C vs. D. Plasma leptin levels changed. A:0.25 ± 1.065 ng/mL; B: -3.42 ± 1.488 ng/mL; C: -3.386± 0.784 ng/mL; D:0.377 ± 1.12 ng/mL. P=0.010 C vs. D. No Adverse side effects were detected in any group. Cyclo-Z containing 15 mg CHP plus 23 mg zinc appears to be the most effective dose and safe for the treatment for both diabetes and obesity through improving insulin resistance and leptin resistance. FDA IND:061897.

Disclosure
M.K. Song: Stock/Shareholder; Self; NovMetapharma Inc in Korea (Investor company).

Funding
NovMetaPharma Co., Ltd.
1182-P: A Selective Nonpeptide Somatostatin Receptor 5 (sst5) Agonist Effectively Decreases Insulin Secretion in the KATPHI Mouse Model
Authors: JULIANA CHRISTINE , CHAI JINGHUA , RICO-BAUTISTA ELIZABETH F. , BETZ STEPHEN F. , DE LEON DIVA D. 
Published: June 2019

Inactivating mutations of β-cell KATP channels cause the most common and severe form of congenital hyperinsulinism (HI), a β-cell disorder that causes dysregulated insulin secretion and persistent hypoglycemia. Children with KATPHI are typically unresponsive to diazoxide, the only FDA-approved drug for HI. Octreotide, a sst2 peptide agonist that inhibits insulin secretion, is used as second line therapy, but poor efficacy and sst2-mediated side effects, such as glucagon suppression and necrotizing enterocolitis, limit its use in infants. Thus, most infants with KATPHI require pancreatectomy for intractable hypoglycemia. To address the unmet need for effective and safe therapies, we examined the ability of a selective sst5 nonpeptide agonist CRN02481 (Crinetics Pharmaceuticals) to suppress insulin secretion and prevent fasting hypoglycemia in the SUR1-/- mouse model of KATPHI. SUR1-/- mouse islets were treated with CRN02481 (100 nM) or vehicle and then stimulated with a physiologic amino acid mixture (4 mM). CRN02481 significantly decreased baseline (1.5 ± 0.2 vs. 2.4 ± 0.5 ng/uL, p≤0.01) and amino acid-stimulated (2.8 ± 1.5 vs. 4.4 ± 1.1 ng/uL, p≤0.05) insulin secretion. SUR1-/- mice were gavaged with CRN02481 (10 mg/kg/day) or PBS for 7 days (n=7/group) and fasting glucose, glucose tolerance and insulin tolerance tests were assessed. CRN02481 significantly increased fasting glucose and prevented fasting hypoglycemia (98 ± 18 vs. 44 ± 6 mg/dL, p&lt;0.00001). During a glucose tolerance test CRN02481 increased post-glucose load glucose concentrations significantly by 60 and 90 minutes. CRN02481 significantly decreased the slope of decline of glucose concentrations after insulin administration (1 u/kg): -2.8 ± 2.3 vs. -5.7 ± 2.1, p=0.03). Collectively these data show that the sst5 agonist CRN02481 effectively suppresses insulin secretion and prevents fasting hypoglycemia in the KATPHI mouse model and is a potentially novel therapy for children with HI.

Disclosure
C. Juliana: Research Support; Self; Crinetics. J. Chai: None. E.F. Rico-Bautista: Employee; Self; Crinetics Pharmaceuticals. Stock/Shareholder; Self; Crinetics Pharmaceuticals. S.F. Betz: Employee; Self; Crinetics Pharmaceuticals. Stock/Shareholder; Self; Crinetics Pharmaceuticals. D.D. De Leon: Consultant; Self; Crinetics, Novartis Pharmaceuticals Corporation, ProSciento, Soleno Therapeutics, Zealand Pharma A/S. Employee; Spouse/Partner; Merck & Co., Inc. Research Support; Self; Crinetics, Dexcom, Inc., Zealand Pharma A/S. Stock/Shareholder; Self; Merck & Co., Inc.

Funding
Crinetics Pharmaceuticals (to D.D.D.)
1184-P: Efficacy of Hydroxychloroquine (HCQ) 400mg in Patients with Poorly Controlled Insulin-Treated Type 2 Diabetes Mellitus
Authors: AHMED RISHAD , SHARMA AMIT BHUSHAN , NATARAJAN A. , AGARWAL DINESH , NARAYANAN A. SHANKAR 
Published: June 2019

Objective: We retrospectively investigated the effects of adding HCQ 400 mg in patients with type 2 diabetes showing sub-optimal control by basal insulin and other OHA therapy.
Method: This is an open label, parallel group, retrospective and multicentre observational study. 123 patients with poorly controlled type 2 diabetes (baseline HbA1c 8.5 ± 0.6%) who are on basal insulin (glargine) with other OHA therapy (metformin 1gm+Sitagliptin 100 mg), were given HCQ 400 mg in addition to insulin. FPG, PPG and HbA1c values, daily insulin dose, body weight and the number of hypoglycemic events were recorded at weeks 0, 12 and 24.
Result: HbA1c decreased by 1.6%, from 8.5 ± 0.6% to 6.9 ± 0.8% (P&lt;0.0001) at 24 weeks. FPG and PPG was reduced significantly from 223.7 ± 31 to 121± 19 mg/dl and from 313.2 ± 41 to 161± 21 mg/dl at the end of 24 week (P&lt;0.0001). Required insulin dose was reduced significantly from 29.4 ± 14.5 to 22.1 ± 12.1 units/day (P= 0.0187). Body weight decreased significantly from 69.5 ± 5.2 to 67.0 ± 6.7 kg, (P= 0.0232). Numbers of hypoglycemic events per patient per month were 0.25 ± 0.35. No severe hypoglycemia occurred during the study period. 56% patients achieved HbA1c ≤ 7% at 24 weeks.
Conclusion: Administration of HCQ 400 mg resulted in sustained improvement in glycemic control when given as an adjunct to insulin therapy in patients with poorly controlled type 2 diabetes.

Disclosure
R. Ahmed: None. A. Sharma: None. A. Natarajan: None. D. Agarwal: None. A. Narayanan: None.
1189-P: Effectiveness of Hydroxychloroquine (HCQ) 400 mg in Uncontrolled T2D Patients on Dual Therapy of Metformin and Sulfonylurea: A Real-World Experience in India
Authors: PURKAIT INDRANIL , PAREEK ANIL , PANNEERSELVAM ARUNACHALAM , MUKHOPADHYAY MONOJIT K. , KUMAR SHARAD , CHANDRATREYA SUJIT ARUN 
Published: June 2019

Objective: Many T2D patients have inadequate glycemic control despite conventional therapy of dual OHAs. Treating such patients in developing countries is a challenge as newer drugs are comparatively costly or patients may have apprehensions for injectable insulin. Objective of this observational study was to evaluate effectiveness of add-on therapy of HCQ in these patients.
Methods: A prospective, observational, multi-centre study was conducted where 1,007 T2D patients (age between 18-65 years), uncontrolled on a combination of two OHAs, with HbA1c ≥7.5%, fasting blood glucose of ≥126 mg/dL or 2-hour blood glucose ≥200 mg/dL and body weight ≥60 kg were prescribed hydroxychloroquine sulphate 400 mg once daily for 24 weeks. Mean change in HbA1c, FBG, PPG, serum creatinine and lipid parameters were assessed.
Results: At week 24, significant reduction in HbA1c (1.29%), FBG (18%), PPG (23%), TC (9%), LDL-C (12%) and non-HDL-C (12%) was observed (p &lt; 0.0001). At the end of 24 weeks, 36.8% patients achieved HbA1c target of &lt;7%.
Conclusion: Hydroxychloroquine effectively improved glycemic and lipid parameters in uncontrolled T2D patients. It may emerge as a valuable therapeutic intervention for patients uncontrolled on two OHAs. Its beneficial effect on lipids may potentially translate to improved CV outcomes.

Disclosure
I. Purkait: Employee; Self; Ipca Laboratories Ltd. A. Pareek: Employee; Self; Ipca Laboratories Ltd. A. Panneerselvam: None. M.K. Mukhopadhyay: None. S. Kumar: Advisory Panel; Self; Abbott, Alere Inc., Alkem Laboratories, Eli Lilly and Company, Eris Lifesciences, Glenmark Pharmaceuticals Limited, Intas Pharmaceuticals Ltd., Johnson & Johnson, Lupin Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi-Aventis, Sun Pharma, Torrent Pharma, USV Private Limited, Wockhardt, Zydus Pharmaceuticals, Inc. Consultant; Self; AstraZeneca, Biocon, Boehringer Ingelheim Pharmaceuticals, Inc., Dr. Reddys Laboratories. S.A. Chandratreya: None.
1219-P: Enhanced Response in Serum Ketone Level in Men Compared with Women by Administration of SGLT2 Inhibitor
Authors: YOSHIDA AKIHIRO , MATSUBAYASHI YASUHIRO , NOJIMA TOSHIAKI , SUGANAMI HIDEKI , KAKU KOHEI , SONE HIROHITO 
Published: June 2019

SGLT2 inhibitors (SGLT2is) reduce hyperglycemia and insulin levels via increased urinary glucose excretion (UGE). Reduced insulin triggers decreased tissue glucose disposal and increased lipid use followed by ketone production. The metabolic response to starvation, the production of beta-hydroxybutyrate (BHB), was reported to be influenced by sex and menopausal status in healthy persons. However, little is known of sex- and menopausal status-specific effects of SGLT2is on BHB. This study investigated the effect of the SGLT2i tofogliflozin on BHB according to sex and menopausal status in type 2 diabetes mellitus (T2DM). Analyzed were 190 T2DM patients taking tofogliflozin as initial monotherapy in a Phase 3 study. Baseline characteristics were: men (66%); premenopausal (7%) and postmenopausal women (27%), age (mean 58y), and mean HbA1c (7.8%), BMI (26kg/m2), BHB (69µmol/L) and eGFR (83mL/min/1.73m2). Sex- and menopausal status-specific differences were analyzed by multivariate analysis. Longer duration of diabetes and lower baseline HDL-C and adiponectin were noted in men while age and HbA1c, BMI, BHB and eGFR were identical between sexes. Increases in BHB at weeks 4 and 52 were: men, median +128%* and +64*, respectively (+ p&lt;0.01 vs. baseline); women, +48* and +58*, respectively. Mean increases in the fasting free fatty acid-to-insulin ratio (FIR) at week 52 were +88%* for men and +53* for women. Reductions in HbA1c and fasting insulin and increases in UGE and free fatty acids at week 52 were similar between sexes. Multivariate analyses showed a greater increase in BHB at week 52 in men than in women, especially postmenopausal women. Further, FIR increased greater in men than in women. Finally, premenopausal women had a greater increase in BHB than postmenopausal women. Results suggest that the different degrees of BHB elevation between sexes via tofogliflozin may provide clinical insights into sex- and menopause-specific metabolic responses to increased lipid use via SGLT2is in T2DM.

Disclosure
A. Yoshida: Employee; Self; Kowa Pharmaceutical Co. Ltd. Y. Matsubayashi: None. T. Nojima: Employee; Self; Kowa Co., Ltd. H. Suganami: Employee; Self; Kowa Co., Ltd. K. Kaku: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk A/S. Speaker's Bureau; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. H. Sone: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kowa Pharmaceutical Europe Co. Ltd., Kyowa Hakko Kirin Co., Ltd., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited.
122-LB: iSage: Successful Basal Insulin Titration Managed by a Prescription-Only Digital Therapy for T2DM
Authors: GRDINOVAC KRISTINE , ROBBINS DAVID C. , LAVENBARG TERI A. , LEVIN PHILIP , SYSKO RYAN 
Published: June 2019

Ideally, initiating and titrating basal insulin should quickly achieve A1C and fasting glucose targets without significant hypoglycemia. In practice, it’s often not so simple.
iSage Rx (iSage) is the first FDA-cleared digital therapy for basal insulin titration that is prescribed by providers and easily downloaded to patients’ mobile phones. In less than a minute, the provider personalizes their patient’s glycemic targets and configures a titration algorithm for use with any basal insulin. The iSage app automatically manages the patient’s titration plan and provides ongoing education regarding insulin administration.
We tested the efficacy of iSage in 27 T2DMs (59±7.6 year, 12M/15F). Entry criteria included T2DM patients treated solely with detemir, glargine or delgudec insulin, fluency in English, and generally healthy. T2DMs with stage 4 or 5 kidney disease, active malignancies, variable glucocorticoid doses, severe visual impairment and dementia were excluded. The study aims included changes in both insulin dose and A1C values while achieving low rates of hypoglycemia. The average (SD) starting and app-directed final doses of insulin were 33.6 (20) and 46.8 (27) U/d, p=0.047, respectively. Initial mean A1c was 8.2 (1.4)% that dropped to 7.3 (0.95)%, p=0.002 at study termination (79-139 days). Among those with an initial A1c &gt;8.0, (mean A1c 9.3%) the final mean A1c was 7.4% (1.0) p=0.005. Of the 2,257 fasting blood glucose readings (BG) recorded in the mobile app, only 27 were &lt;70 mg/dL (1.64% of total fasting BGs). Participants required almost no unexpected visits or phone consultations to manage their insulin doses.
The iSage digital therapy, while prescribed by a provider, requires minimal provider demands, is patient self-directed, and produces significant reductions in A1C with low rates of hypoglycemia.

Disclosure
K. Grdinovac: None. D.C. Robbins: None. T.A. Lavenbarg: None. P. Levin: Research Support; Self; MannKind Corporation, Novartis AG, Novo Nordisk Inc. Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Lilly Diabetes, Merck & Co., Inc., Sanofi. R. Sysko: Employee; Self; iSage Rx, LLC.

Funding
Amalgam Rx, Inc.; Blue KC
1227-P: GlycoMark 1,5-Anhydrocluitol Values in Patients Taking SGLT2 Inhibitors
Authors: FEREIDOUNI SAM S. , SHOWS THOMAS P. , LESSARD-CHAUDOIN CHANTELLE , BRABENTZ KIM , TENOPALA ROBERTO E. , DAHLEN JEFFREY R. 
Published: June 2019

The GlycoMark test measures 1,5-anhydroglucitol (1,5-AG), which is an indicator of hyperglycemic excursions over the prior 1-2 weeks in patients with diabetes. Circulating serum levels of 1,5-AG decrease in response to significant hyperglycemia because glycosuria interferes with 1,5-AG reabsorption in the kidney tubules. Significant hyperglycemia and resultant glycosuria causes 1,5-AG levels to fall below the normal range (∼10 ug/mL), and persistent glycosuria is associated with very low 1,5-AG levels, less than or equal to 2 ug/mL. SGLT2 inhibitors elicit their effect by blocking glucose reabsorption, causing persistent glycosuria. A survey of clinical laboratory results in 2014 indicated that 13% of the GlycoMark 1,5-AG tests produced results of 2 ug/mL or less (unpublished, data on file). We hypothesized that the use of SGLT2 inhibitors (SGLT2i) would produce a high frequency of GlycoMark 1,5-AG results less than 2 ug/mL. A review of GlycoMark 1,5-AG measurements performed between January 2015 - April 2018 from 291 patients that were prescribed SGLT2i was performed. 35 patients were found to be non-compliant with their SGLT2i and were excluded from the analysis. From the remaining 256 patients taking SGLT2i, the average GlycoMark 1,5-AG level was 1.7 ug/mL and 87% of patients taking SGLT2 inhibitors had GlycoMark 1,5-AG values less than or equal to 2 ug/mL. The results of this analysis indicate that the majority of patients with diabetes that are taking SGLT2i have very low GlycoMark 1,5-AG results, which reflects the persistent glycosuria caused by the SGLT2i. In patients taking SGLT2i, a GlycoMark 1,5-AG result of 2 ug/mL may be useful as an indicator of the SGLT2i effect, particularly in patients with moderate to good glycemic control. Additionally, the average GlycoMark 1,5-AG level in the 35 non-compliant patients was 7.5 ug/mL, suggesting that GlycoMark test measurements above 2 ug/mL should be investigated for non-compliance, interference with, or reduced effectiveness of SGLT2i.

Disclosure
S.S. Fereidouni: Advisory Panel; Self; AstraZeneca, Janssen Pharmaceuticals, Inc. Consultant; Self; glycomark. Speaker's Bureau; Self; Amgen Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc. T.P. Shows: None. C. Lessard-Chaudoin: None. K. Brabentz: None. R.E. Tenopala: None. J.R. Dahlen: Employee; Self; GlycoMark.
1233-P: Systematic Literature Review (SLR) and Network Meta-analysis (NMA) of SGLT-1/2 Inhibitors vs. Metformin (MET) as Add-On to Insulin in T1DM
Authors: LANGFORD BRYONY E. , EVANS MARC , HASKINS-COULTER TAO , O'CONNOR MARY-ELLEN , CANT HARRIET E. , EDDOWES LUCY A. , EDMONDS CHRISTOPHER , TANK AMARJEET 
Published: June 2019

T1DM is characterized by deficient insulin production, requiring multiple daily insulin doses. However, glycemic control is often suboptimal, and insulin-associated weight gain and hypoglycemia are concerns. Therefore, adjunctive therapy may be beneficial. A SLR with searches conducted to 16 Oct 2018 identified phase III/IV RCTs of MET or SGLT1/2 inhibitors as add-on to insulin in T1DM. MEDLINE, Embase and the Cochrane Library were searched, as well as congresses, reference lists and grey literature. Bayesian NMAs were performed at Week 24/26 (Week 24) and Week 52 (Week 52) for change from baseline in HbA1c and weight, and the proportion of participants experiencing hypoglycemic events and hypoglycemic severe adverse events. Nine placebo (PBO) controlled RCTs of dapagliflozin (DAPA), MET, sotagliflozin (SOTA) or empagliflozin (EMPA) reporting results were included. There was some evidence of heterogeneity in study design and outcomes. Results of the NMAs for MET vs. comparator (Table) found that the SGLT2 and SGLT1/2 inhibitors generally performed better than MET for HbA1c and weight, but there were few significant differences for hypoglycemia at Week 52. Results suggest that adjunctive use of SGLT2 and SGLT1/2 inhibitors including DAPA can improve glycemic control compared to MET while enabling weight loss in T1DM, and demonstrate consistent efficacy for the class.

Disclosure
B.E. Langford: Employee; Self; Costello Medical. Research Support; Self; AstraZeneca. M. Evans: Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Mundipharma, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sunovion Pharmaceuticals Inc. T. Haskins-Coulter: Employee; Self; Costello Medical. M. O'Connor: Employee; Self; Costello Medical. H.E. Cant: Employee; Self; Costello Medical. L.A. Eddowes: Employee; Self; Costello Medical. C. Edmonds: Employee; Self; AstraZeneca. A. Tank: Employee; Self; AstraZeneca.

Funding
AstraZeneca; Cambridge University