Dulaglutide Research Articles

Long-Term Effectiveness and Safety of Once Weekly Dulaglutide as Add-on to Metformin or Metformin Plus Insulin Secretagogues in Obesity and Type 2 Diabetes

Aim of this monocentric retrospective observational study was to evaluate the 18-month effectiveness and safety of once weekly 1.5 mg GLP-1 receptor agonist (GLP-1 RA) dulaglutide (DU) as add-on to metformin (MET) or MET plus conventional insulin secretagogues (SFU/glinide) in a study cohort with excess body weight (BW) and type 2 diabetes (T2D). Comparative efficacy versus once daily 1.2/1.8 mg liraglutide (LIRA) in a study sample naïve to GLP-1 RAs, matching for age, gender, BMI, T2D duration, cardiovascular comorbidities and medications, was addressed as a secondary aim. Clinical and biochemical data for efficacy outcomes and information on drug discontinuation due to adverse events (AEs) were collected from digital records. Initial analysis included 126 overweight and obese T2D patients (48.4% females). Out of these, 13 discontinued DU due to moderate-severe gastrointestinal AEs after a median follow-up of 6 (3 to 8) months, while 65 completed 18 months of continuous therapy. At 6 months, there was a significant median HbA1c reduction of -0.9 (-1.50 to -0.20) % with respect to baseline values (p<0.001), which remained stable during 18 months of follow-up. These results were accompanied by a moderate BW loss sustained over time, with a median reduction of -1.16 (-4,29 to 0.45) % at 6 months and -1.47 (-4.2 to 0.72) % at 18 months (p=0.048). At univariate Spearman analysis, a negative correlation between baseline BMI and risk of drug discontinuation due to gastrointestinal AEs was observed. The protective effect of obesity (BMI ≥ 30kg/m2) against drug discontinuation was confirmed by an exploratory logistic regression analysis, while adjusting for confounders [OR 0.211 (95%CI 0.058–0.771), p=0.019]. Neither gender, nor age, nor T2D duration, nor concomitant SUF/glinide use, nor shifting to DU from other GLP-1 RAs influenced its long-term effectiveness. However, higher baseline HbA1c values emerged as predictors of clinically relevant efficacy outcomes, either in form of HbA1c reduction ≥ 0.5% [OR 2.961 (95%CI 1.394–6.290), p=0.005] or BW loss ≥ 5% [OR 2.571 (95%CI 1.171–5.644), p=0.019]. The efficacy outcomes were corroborated by head-to-head comparison with LIRA, a GLP-1 RA with durable beneficial effects on glycemic control and BW in real word scenarios (1). With the advantage of once weekly administration, at 18-month follow-up, a significant larger fraction of patients on DU therapy reached glycemic targets (HbA1c ≤ 7.0%) when compared to those on LIRA: from 14.8% at baseline (both groups) to 64.8% with DU and 42.6% with LIRA (p=0.033). Although limited by a retrospective design and lack of constant up-titration for LIRA to the highest dose, these findings indicate that the beneficial glycometabolic responses to DU on a background of MET or MET plus SFU/glinide are durable, especially in presence of obesity and greater HbA1c impairment.(1) Ref: Mirabelli et al. IJERPH. 2019;17(1):207.

Clinical Effectiveness and Safety of Once-Weekly GLP-1 Receptor Agonist Dulaglutide as Add-On to Metformin or Metformin Plus Insulin Secretagogues in Obesity and Type 2 Diabetes.

Aims and methods: The aim of this monocentric retrospective observational study was to evaluate the 18-month safety and effectiveness of GLP-1 receptor agonist (GLP-1 RA) dulaglutide (DU) 1.5 mg/once weekly as an add-on to metformin (MET) or MET plus conventional insulin secretagogues in a study cohort with excess body weight and type 2 diabetes (T2D). Comparative efficacy versus liraglutide (LIRA) 1.2–1.8 mg/once daily in a study sample naïve to GLP-1 RAs, frequency matching for age, gender, T2D duration, degree of glycemic impairment, cardiovascular comorbidities, and medications, was addressed as a secondary aim. Clinical and biochemical data for efficacy outcomes and information on drug discontinuation due to adverse events (AEs) were collected from digital records. Results: Initial analysis included 126 overweight and obese T2D patients (48.4% females). Out of these, 13 discontinued DU due to moderate–severe gastrointestinal AEs after a mean follow-up of 6 (4 standard deviations (SD)) months, while 65 completed 18 months of continuous therapy. At 6 months, there was a significant mean HbA1c reduction of −0.85% (1.17 SD) with respect to baseline values (p < 0.001), which remained stable during 18 months follow-up. These results were accompanied by a moderate weight loss sustained over time, with a mean reduction of −2.0% (4.3 SD) at 6 months and −1.3% (4.8 SD) at 18 months (p = 0.091). At univariate analysis, a negative correlation between baseline body mass index (BMI) and risk of drug discontinuation due to gastrointestinal AEs was observed. The protective effect of obesity against drug discontinuation was confirmed by logistic regression analysis. Neither gender, nor age, nor T2D duration, nor concomitant conventional insulin secretagogue use, nor switching to DU from other GLP-1 RAs influenced its long-term effectiveness. However, higher baseline HbA1c values emerged as predictors of clinically relevant efficacy outcomes, either in terms of HbA1c reduction ≥ 0.5% or body weight loss ≥ 5%. The efficacy outcomes were corroborated by head-to-head comparison with LIRA, a GLP-1 RA with durable beneficial effects on glycemic control and body weight in real-world experiences. With the advantage of once-weekly administration, at 18-month follow-up, a significantly larger fraction of patients on DU therapy reached glycemic targets (HbA1c ≤ 7.0%) when compared to those on LIRA: from 14.8% at baseline (both groups) to 64.8% with DU and 42.6% with LIRA (p = 0.033). Conclusions: Although limited by a retrospective design and lack of constant up-titration for LIRA to the highest dose, these findings indicate that the beneficial responses to DU on a background of MET or MET plus insulin secretagogues are durable, especially in the presence of obesity and greater HbA1c impairment.

Clinical Outcomes by Albuminuria Status with Dulaglutide versus Insulin Glargine in Participants with Diabetes and CKD: AWARD-7 Exploratory Analysis.

In the AWARD-7 trial of participants with type 2 diabetes (T2DM) and moderate-to-severe CKD, dulaglutide (DU) treatment slowed decline in eGFR compared with insulin glargine (IG). Treatment with doses of either DU or IG resulted in similar levels of glycemic control and BP. The aim of this analysis was to determine the risk of clinical event outcomes between treatment groups. Participants with T2DM and CKD categories 3-4 were randomized (1:1:1) to 0.75 or 1.5 mg DU weekly or IG daily as basal therapy, with titrated insulin lispro, for 1 year. The time to occurrence of the composite outcome of ≥40% eGFR decline, ESKD, or death due to kidney disease was compared using a Cox proportional-hazards model. Patients treated with 1.5 mg DU weekly versus IG daily for 1 year had a lower risk of ≥40% eGFR decline or ESKD events in the overall study population (5% versus 11%; hazard ratio, 0.45; 95% CI, 0.20 to 0.97; P=0.04). Most events occurred in the subset of patients with macroalbuminuria, where risk of the composite outcome was substantially lower for 1.5 mg DU versus IG (7% versus 22%; hazard ratio, 0.25; 95% CI, 0.10 to 0.68; P=0.006). No deaths due to kidney disease occurred. Treatment with 1.5 mg DU weekly was associated with a clinically relevant risk reduction of ≥40% eGFR decline or ESKD compared with IG daily, particularly in the macroalbuminuria subgroup of participants with T2DM and moderate-to-severe CKD.

Semaglutide cost effective versus dulaglutide in Japan

Semaglutide cost effective versus dulaglutide in Japan

Dulaglutide and Cognitive Impairment in Type 2 Diabetes

Diabetes is a risk factor for cognitive impairment. This study, an exploratory analysis of the larger Researching Cardiovascular Events with a Weekly

Switching from liraglutide to dulaglutide, is it worth it?: Outcomes at 24 weeks follow-up

Switching from liraglutide to dulaglutide, is it worth it?: Outcomes at 24 weeks follow-up

357-OR: Efficacy and Safety of Dulaglutide 3mg and 4.5mg vs. Dulaglutide 1.5mg: 52-Week Results from AWARD-11

Dulaglutide (DU) is approved at 2 doses (0.75 and 1.5 mg) for treatment of T2D. In this phase 3 study, once weekly DU 3 mg and 4.5 mg were compared to DU 1.5 mg for efficacy and safety through 52 weeks (wks) (primary endpoint at 36 wks) in patients with inadequately controlled T2D on metformin therapy. Patients were randomized (1:1:1) to once weekly DU 1.5 mg (n=612), DU 3 mg (n=616), and DU 4.5 mg (n=614). All patients were initiated on once weekly DU 0.75 mg for 4 wks, followed by step-wise dose escalation every 4 wks to the randomized dose of 1.5 mg, 3 mg, or 4.5 mg. Efficacy measures were analyzed based on data on-treatment without initiation of rescue medication. Mean age was 57.1 yrs, mean baseline (BL) A1C was 8.6%, and mean BL body weight (BW) was 95.7 kg. DU 1.5 mg, 3 mg and 4.5 mg showed significance (p&amp;lt;0.001) compared to BL for A1C, BW and fasting serum glucose (Table). DU 3 mg and 4.5 mg were both superior to DU 1.5 mg at the 36 wk primary endpoint, and remained significantly greater at 52 wks, for improvements in measures of glycemic control and body weight (Table). As expected for the GLP-1 receptor agonist class, commonly reported adverse events were nausea, diarrhea, and vomiting (Table). There were no new safety findings with the higher DU doses. In conclusion, escalation from DU 1.5 mg to DU 3 mg or 4.5 mg provided clinically relevant, dose-related improvements in glycemic control and body weight with an acceptable safety profile. Disclosure J.P. Frias: Consultant; Self; Eli Lilly and Company, Gilead Sciences, Inc., LifeScan, Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Allergan plc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb, Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk A/S, Pfizer Inc., Sanofi. Speaker’s Bureau; Self; Merck &amp; Co., Inc., Sanofi. E. Bonora: Advisory Panel; Self; Lilly Diabetes, Novartis AG, Sanofi. Speaker’s Bureau; Self; Abbott, Lilly Diabetes, Novo Nordisk A/S, Sanofi. L.A. Nevarez Ruiz: None. G. Li: Employee; Self; Eli Lilly and Company. Z. Yu: None. Z. Milicevic: Employee; Self; Eli Lilly and Company. R. Malik: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. A. Bethel: Employee; Self; Eli Lilly and Company. D. Cox: Employee; Self; Eli Lilly and Company.

924-P: Exploring Potential Mediators of the Cardiovascular Benefit of Dulaglutide in REWIND

The REWIND trial showed that relative to placebo (PL), once weekly dulaglutide (DU) 1.5 mg reduced the incidence of a major adverse cardiovascular (CV) event (MACE; nonfatal myocardial infarction, nonfatal stroke, or CV death) in patients with T2D with and without established CV disease (hazard ratio (HR) 0.88, 95% CI [0.79, 0.99]; p=0.026). DU also significantly reduced A1C, body weight (BW), and systolic blood pressure (SBP) (Table). In this post-hoc assessment, a mediation analysis was used to estimate the degree to which the effect of DU on these risk factors could statistically account for its effect on MACE. Data were analyzed from 9901 patients who had 1257 first MACE events over 5.4 median yrs of observation. Those risk factors for which the updated mean on follow-up was significantly related to MACE were added to a separate Cox model that included DU allocation, the baseline [BL] value of the measurement and the updated mean of the variable as time dependent covariates. Only A1C satisfied this condition (Table), suggesting that BW and SBP did not mediate the effect of DU on MACE in this study population. The effect size of DU on the MACE outcome was attenuated by 36.1% after accounting for its effect on A1C (Table). In conclusion, the results suggest most of the CV benefit of DU on MACE is not attributable to the A1C, BW, or SBP-lowering effects of DU. Disclosure H.M. Colhoun: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Regeneron Pharmaceuticals, Sanofi-Aventis. Research Support; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc., Novo Nordisk Inc., Pfizer Inc., Regeneron Pharmaceuticals, Sanofi-Aventis. Speaker’s Bureau; Self; Eli Lilly and Company, Regeneron Pharmaceuticals, Sanofi. Stock/Shareholder; Self; Bayer AG, Roche Pharma. Other Relationship; Self; Eli Lilly and Company, Sanofi. C. Hasenour: Employee; Self; Eli Lilly and Company. M.C. Riddle: Consultant; Self; ADOCIA, Dance Biopharm Holdings, Inc., GlaxoSmithKline plc., Sanofi US, Theracos, Inc. Research Support; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc. K. Branch: Consultant; Self; Bayer AG. Research Support; Self; Bayer AG, Eli Lilly and Company. M. Konig: Employee; Self; Eli Lilly and Company. C. Atisso: Employee; Self; Eli Lilly and Company. M. Lakshmanan: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. R. Mody: Employee; Self; Eli Lilly and Company. H.C. Gerstein: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi. Consultant; Self; Kowa Pharmaceuticals America, Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi. Other Relationship; Self; Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Sanofi.

2188-PUB: Efficacy and Safety in Chinese T2D Patients Discontinued from OAM to Once-Weekly Dulaglutide Monotherapy

Background and Objective: GLP-1RAs including dulaglutide (DU) are recommended as 1st injectable therapy in T2D patients after oral antihyperglycemic medicine (OAM) failure. Efficacy and safety of DU have been studied when adding on OAMs, but not in Chinese population discontinued from OAM. This is the first post-hoc analysis to evaluate the efficacy and safety of DU in Chinese T2D patients discontinued from OAM and started with once weekly DU. Methods: A total of 292 Chinese patients who discontinued from OAM monotherapy in AWARD-CHN1 study (NCT01644500) were included in this post-hoc analysis as modified intent-to-treat (mITT) population. Results: Overall, the mITT population had mean age of 55.0 years, with 5.5 years’ mean duration of T2D at baseline. Previous OAM treatment included metformin, acarbose, sulfonylureas, and meglitinides. Table 1 summarized the efficacy and safety outcomes at Week 26. DU 1.5 mg was superior to glimepiride for HbA1c and body weight reduction. Greater improvement in beta cell function was observed for both DU groups, along with fewer hypoglycemia events. The most common adverse events for DU were gastrointestinal in nature, including diarrhea, abdominal distension, vomiting and nausea. Conclusion: DU is effective and safe for Chinese T2D patients discontinued from OAM and can further improve glucose control and protect beta cell function compared to glimepiride. Disclosure Y. Li: None. B. Zhang: Employee; Self; Eli Lilly and Company. S. Liu: Employee; Self; Eli Lilly and Company.

928-P: Dulaglutide Has Higher Adherence and Persistence than Semaglutide and Exenatide QW: 6-Month Follow-Up from U.S. Real-World Data

The objective of this retrospective real-world observational study was to compare 6-month (mo) adherence and persistence among patients (pts) initiating weekly GLP-1 receptor agonists (GLP-1RA), dulaglutide (DU) vs. semaglutide (SEMA) or DU vs. exenatide QW (EQW) BCise pen in the U.S., using claims from the HealthCore Integrated Research Database (HIRD®) between August 2017 and June 2019 (index date=earliest GLP-1RA fill date). Pts ≥18 yrs old, with T2D, no claim for GLP-1 RAs in the 6 mos pre-index period, ≥1 claim for DU, SEMA or EQW during the index period, and continuous enrollment 6 mos pre- and post-index were included. DU users were propensity-matched 1:1 to SEMA (3,852 pairs) or EQW (1,879 pairs) users. Matched cohorts (DU:SEMA/DU:EQW) were balanced in baseline characteristics and the mean age was 54/55 years with approximately 49/51% males, respectively. At 6 mos, DU users were more likely to be adherent [Proportion of Days Covered (PDC)≥80%] than SEMA (odds ratio [OR]=1.986, 95% CI=[1.81, 2.18]) or EQW users (2.06 [1.81, 2.34]) (table). Cox regression showed that DU users were less likely to discontinue therapy than SEMA (hazard ratio [HR]= 0.71, 95% CI=[0.66, 0.76]) or EQW users (0.59 [0.53, 0.65]) (table). At 6-mos follow-up, pts initiating DU had higher medication adherence, and were more persistent to their treatment, compared to pts initiating either SEMA or EQW. Disclosure R. Mody: Employee; Self; Eli Lilly and Company. M. Yu: Employee; Self; Eli Lilly and Company. Employee; Spouse/Partner; LifeLabs. Stock/Shareholder; Self; Eli Lilly and Company. B.K. Nepal: None. M. Konig: Employee; Self; Eli Lilly and Company. M. Grabner: Research Support; Self; Eli Lilly and Company.

1055-P: Glycemic Variability with Dulaglutide vs. Basal Insulin Glargine

Reductions in glycemic variability (GV) may be associated with decrease in cardiovascular complications. This analysis assessed GV in people with type 2 diabetes receiving dulaglutide (DU) 1.5 mg once weekly or basal insulin glargine (IGlar) in two clinical trials. AWARD (AW) 2 participants on metformin and glimepiride randomized to DU (N=173) or IGlar (N=161). AW9 participants randomized to DU (N=127) or placebo (N=120), both added to IGlar with/without metformin. GV measured at baseline and study endpoint (AW2: week 26; AW9: week 28). Studies analyzed separately for within-day and between-day GV from self-monitored blood glucose (SMPG), and between-day GV from fasting self-measured plasma glucose (FSMPG), by standard deviation (SD). AW2 DU and IGlar arms were 54% and 51% male at baseline; mean (SD) HbA1c of 8.2 (1.0) and 8.1 (0.9) %; fasting plasma glucose (FPG) 162.0 (46.7) and 161.1 (47.1) mg/dL. DU treatment yielded significantly greater reductions in within-day SMPG GV (Figure) than IGlar. AW9 DU+IGlar and Placebo+IGlar arms included 58% and 58% male participants; mean (SD) HbA1c was 8.4 (0.8) and 8.2 (0.8) %; FPG 154.5 (46.5) and 155.0 (46.7) mg/dL. DU+IGlar showed significantly greater reductions in within-day and between-day GV from SMPG (Figure), and between-day FSMPG GV than placebo+IGlar. DU treatment showed a greater reduction in within-day SMPG GV versus IGlar. DU+IGlar reduces SMPG GV and FSMPG GV more than placebo+IGlar. Disclosure E. Jodar: Other Relationship; Self; Elli Lilly &amp; Co, Novo Nordisk, MSD, Lilly, Janssen, Pfizer, AstraZeneca, Sanofi, UCB, Amgen, FAES, Shire, Mundipharma, Novartis. I. Romera: Employee; Self; Eli Lilly and Company. Q. Wang: Employee; Self; Eli Lilly and Company. E. Caveda: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. L. Garcia: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Funding Eli Lilly and Company

929-P: Dulaglutide Shows Sustained A1C Reduction: Two-Year U.S. Real-World Study

The primary objective of this retrospective, observational study was to evaluate glycemic control over a 2 yr follow-up period among dulaglutide (DU) initiators with continuous treatment using U.S. claims data from the HealthCore Integrated Research Database (HIRD®) between May 2014 and May 2019 (index date=earliest DU fill during index period between November 2014 and May 2017). Patients (pts) ≥18 yrs old with T2D, ≥1 pharmacy claim for DU during the index period, continuous enrollment in the 6 months pre index (=baseline [BL]) and 2 yrs post index, ≥1 claim for DU or ≥60 days supply in every quarter during the 2-yr follow-up period, and ≥1 A1C result at both BL and 2 yrs were included. At BL, pts (N=872; 47.5% female) were (mean ± SD) 54.5 ± 8.2 yrs old with an A1C of 8.7 ± 1.8%. Antihyperglycemic medication use pre/post index included: insulin, 28%/35%; DPP-4 inhibitors, 37%/20%; SGLT2 inhibitors, 29%/44%. More than two-thirds were being treated for dyslipidemia, hypertension, or CVD. Key results are included in the Figure. Significant A1C reduction was observed from BL to 2 yrs (-1.3%, p&amp;lt;0.0001). Forty-three percent of pts achieved an A1C &amp;lt;7% and 74% achieved an A1C &amp;lt;8% at 2 yrs. In this real-world study among DU initiators with continuous treatment, a clinically significant reduction in A1C was seen at the 3-month assessment and persisted for up to 2 yrs. These data support the use of DU as an effective long-term treatment for T2D in clinical practice. Disclosure R. Mody: Employee; Self; Eli Lilly and Company. M. Yu: Employee; Self; Eli Lilly and Company. Employee; Spouse/Partner; LifeLabs. Stock/Shareholder; Self; Eli Lilly and Company. M. Grabner: Research Support; Self; Eli Lilly and Company. K. Boye: Employee; Self; Lilly Diabetes. Stock/Shareholder; Self; Eli Lilly and Company. C. Teng: Research Support; Self; Eli Lilly and Company. A. Kwan: Employee; Self; Eli Lilly and Company. Employee; Spouse/Partner; Eli Lilly and Company. Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company.

950-P: Efficacy and Safety of Once-Weekly Dulaglutide Added to Titrated Insulin Glargine, Prandial Insulin, and Oral Agents in Obese Asian T2 Diabetes (T2D) Patients: One Year Real-World Evidence from India

Objective: To assess the effect of the addition of a weekly GLP-1 Receptor Agonist, injection Dulaglutide (DU) 1.5mg in obese T2D patients, sub-optimally controlled on titrated basal insulin Glargine (iGL), prandial insulin (iP), metformin and glimepiride (SU). Methods: We retrospectively observed the impact of addition of DU in 167 patients with HbA1c ≥ 8% for ≥ 16 weeks (wk), all on titrated iGL and also on metformin (n=156; 1.5-2g/d), SU (n=101; 3-4mg/d) and iP (n=75; 10-14 units/d). End points were changes in (i) HbA1c (ii) body weight (iii) doses of iGL and iP (iv) dose of SU at wk 16, 32 and 52. Adverse events and side effects of the combination of DU and iGL were noted. Results: One hundred sixty-seven patients (89M/78F, age 50±4.5 years, wt.82.8±1.4 kg, BMI 30.1±2.1kg/m2, eGFR 78±4mL/min./1.73m2, 10.3±1.1 years duration of T2D) met the inclusion criteria. After addition of DU, HbA1c was - 1.23% [8.24±0.3 to 7.01±0.2, P&amp;lt;0.0001] at wk 16 in 74 % patients, which decreased to 6.9±0.3% (P=0.1586) in 16% at wk 32, but rose to 7.1±0.1% (P=0.1885) in 10% at wk 42-52. At wk 16, weight was - 2.3 kg (82.8±1.4 to 80.5±1.6, P&amp;lt;0.0001) in 78% patients with a further loss of 1.1±0.7 kg (P&amp;lt;0.0001) in 12% by wk 32, but was stable in others until wk 52. Dose of iGL was - 11.1 units (41.3±10.2 to 30.2±9.1, P=0.0381) in 65% subjects by wk 32, was stable in 28% but rose by 4.1±0.01 units (P=0.0078) in 7% by wk 52. Dose of iP was -5.9±0.03 units (12.5±0.3 to 6.6±0.2, P=0.9700) in 31% patients. Dose of SU had to be reduced by 60% in 75% patients and had to be stopped in others because of minor hypoglycemia. No major hypoglycemia occurred. Side effects with DU were nausea (16.5%), vomiting (15.9%) and diarrhea (6.8%), but none had to stop therapy. Conclusion: Weekly DU when added to iGL, provides statistically significant glycemic control with weight loss, reduced hypoglycemia risk and insulin doses. This combination therapy is well tolerated. Disclosure A. Nigam: Advisory Panel; Self; Intas Pharmaceuticals Ltd., Lupin Pharmaceuticals, Inc., Sun Pharmaceutical Industries Ltd., Torrent Pharmaceuticals, USV Private Limited. Speaker’s Bureau; Self; AstraZeneca, Biocon, Cipla Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi.

356-OR: Effect of Dulaglutide on Kidney Function–Related Outcomes in Type 2 Diabetes: Post Hoc Analysis from the REWIND Trial

In participants with type 2 diabetes (T2D) in the REWIND trial, dulaglutide (DU) use for median follow-up of 5.4 years was associated with reduced composite renal outcomes, defined as the first occurrence of new macroalbuminuria, sustained decline in estimated glomerular filtration rate (eGFR) of ≥30%, or chronic renal replacement therapy. The objective of this post-hoc analysis was to evaluate the effect of dulaglutide on renal outcomes related to kidney function that are typically used in renal outcomes studies, defined as the composite endpoint of sustained eGFR decline ≥40%, end-stage renal disease (ESRD), or all-cause death. Participants with T2D at cardiovascular (CV) risk were randomized (1:1) to DU 1.5 mg once-weekly or placebo. This post-hoc analysis used Cox proportional hazards modeling for time to first event to determine the risk of renal outcomes. Sensitivity analyses were conducted by replacing the all-cause death component with CV or renal death, or renal death. At baseline, treatment groups had similar eGFR (mean±SD: DU=77.2±22.7; placebo=76.6±22.8). The incidence rate of the composite endpoint was significantly lower for the DU group compared with placebo (Table). Treatment with DU 1.5 mg was associated with a 17% risk reduction in kidney function-related outcomes, suggesting potential delay in progression of diabetic kidney disease in patients with T2D at CV risk. Disclosure J.E. Shaw: Advisory Panel; Self; AstraZeneca, Merck Sharp &amp; Dohme Corp., Mylan, Sanofi. Research Support; Self; AstraZeneca. Speaker’s Bureau; Self; Eli Lilly and Company, Mylan. F.T. Botros: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. R. Malik: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. C. Atisso: Employee; Self; Eli Lilly and Company. H.M. Colhoun: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Regeneron Pharmaceuticals, Sanofi-Aventis. Research Support; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc., Novo Nordisk Inc., Pfizer Inc., Regeneron Pharmaceuticals, Sanofi-Aventis. Speaker’s Bureau; Self; Eli Lilly and Company, Regeneron Pharmaceuticals, Sanofi. Stock/Shareholder; Self; Bayer AG, Roche Pharma. Other Relationship; Self; Eli Lilly and Company, Sanofi. H.C. Gerstein: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi. Consultant; Self; Kowa Pharmaceuticals America, Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi. Other Relationship; Self; Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Sanofi. Funding Eli Lilly and Company

1056-P: Effect of Dulaglutide on Glycemic Variability: Post Hoc Analysis of the AWARD Studies

Glycemic variability (GV) may contribute to the development and progression of cardiovascular complications. This post-hoc analysis assessed GV in people with type 2 diabetes, treated with once-weekly dulaglutide (DU), and not receiving any concomitant insulin treatment. Analysis included pooled data from 5 randomized, parallel-arm, phase 3 studies (AWARD 1,2,3,6 and 8). The participants (N=1114, 48% male) received DU 1.5 mg without any concomitant insulin for 26 weeks and with evaluable GV measurements at baseline and study endpoint (week 26). The measurements included within-day and between-day GV calculated by standard deviation (SD) and coefficient of variation (CV) from self-monitored plasma glucose (SMPG), and between-day fasting self-monitored plasma glucose (FSMPG) values. At baseline, the mean (SD) age was 55.9 (9.7) years, BMI 32.7 (5.2) kg/m2, HbA1c 8.0 (0.9) % and fasting plasma glucose 166.5 (47.8) mg/dL. At 26 weeks, DU significantly reduced within-day and between-day GV from SMPG values (SD values, p&amp;lt;0.001, Figure) and between-day GV from FSMPG (p&amp;lt;0.001). SMPG GV changes were significant and consistent across studies. Analysis by CV gave consistent results (Figure). Overall, the analysis suggests that treatment with once-weekly DU 1.5 mg reduces within-day and between-day GV from SMPG and between-day GV from FSMPG. Disclosure E. Jodar: Other Relationship; Self; Elli Lilly &amp; Co, Novo Nordisk, MSD, Lilly, Janssen, Pfizer, AstraZeneca, Sanofi, UCB, Amgen, FAES, Shire, Mundipharma, Novartis. Q. Wang: Employee; Self; Eli Lilly and Company. I. Romera: Employee; Self; Eli Lilly and Company. E. Caveda: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. L. Garcia: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Funding Eli Lilly and Company

OR30-06 Assessment of Dulaglutide Safety in Older Patient Populations in Rewind

Background: Dulaglutide (DU) was superior to placebo (PL) in reducing the incidence of Major Adverse Cardiovascular Events in the Researching Cardiovascular Events with a Weekly INcretin in Diabetes (REWIND Study) broad patient population. The safety of DU treatment is also of interest to health care providers who treat an older patient population (≥65 years of age). Aims: The primary objective of this post-hoc analysis was to evaluate DU safety in the REWIND patient subgroup populations categorized by age (≥ 65 and < 65 years) with regards to the occurrence of the composite safety outcome of overall mortality and severe hypoglycemia. One of the key secondary objectives was first occurrence of severe hypoglycemia. Methods: Patients were grouped into two age groups: ≥65 and <65 years. Time-to-event for the composite safety endpoint as well as individual variables were analyzed using Cox proportional hazards regression. Hazard ratios (HRs) and 95% confidence intervals (CIs) for between group treatment differences were also calculated. Results: Of the 9,901 patients randomized in REWIND, a total of 5,256 (DU, 2,619; PL, 2,637) were aged ≥65 years. The incidence of the composite safety outcome for patients aged ≥65 years was 399 of 2619 (15.2%) for DU-treated patients and 425 of 2,637 (16.1%) for PL-treated patients. The incidence of the composite safety outcome for those aged <65 years was 188 of 2,330 (8.1%) for DU-treated patients and 224 of 2,315 (9.7%) for PL-treated patients. Between group treatment differences (HR [95% CI]) were 0.94 (0.82, 1.08) for patients ≥65 years of age and 0.82 (0.68, 1.00) for patients <65 years of age; interaction p-value = 0.277. The incidence of the secondary outcome of first occurrence of severe hypoglycemia for patients aged ≥65 years was 46 of 2619 (1.8%) for DU-treated patients and 49 of 2,637 (1.9%) for PL-treated patients. The incidence of this outcome for patients <65 years was 18 of 2,330 (0.8%) for DU-treated patients and 25 of 2,315 (1.1%) for PL-treated patients. Between group treatment differences (HR [95% CI]) were 0.95 (0.63, 1.42) for patients ≥65 years of age and 0.71 (0.39, 1.31) for patients <65 years of age; interaction p-value = 0.443. The safety profile of DU was reviewed based upon the results of subgroup analysis of treatment emergent adverse events and serious adverse events by preferred terms for comparing PL and DU for age subgroups (≥65 years of age versus <65 years). None of the results indicated that DU has a different safety profile across the age subgroups evaluated in this post-hoc analysis. Conclusions: Treatment with DU demonstrated similar safety in REWIND patients aged ≥65 years and those aged <65 years. Dulaglutide can be considered a safe and effective treatment option for use in older adults.

Дулаглутид – новое в лечении сахарного диабета 2 типа

Дулаглутид – новое в лечении сахарного диабета 2 типа

In patients ≥ 50 years with type 2 diabetes and CV disease or risk factors, dulaglutide reduced CV outcomes.

Source Citation Gerstein HC, Colhoun HM, Dagenais GR, et al; REWIND Investigators. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled...

Dulaglutide Prevents Some Adverse Cardiovascular Outcomes in Patients with Diabetes

Glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors prevent some adverse cardiovascular (CV) events in

2303-PUB: Efficacy of Dulaglutide (DU) as First Injectable Option for Patients with Type 2 Diabetes (T2D): A Post Hoc Pooled Analysis

Background: ADA-EASD consensus report recommends using GLP-1RAs including DU as 1st injectable therapy prior to basal insulin in most patients with T2D not at their glycemic goals after oral antidiabetic medications (OADs). Objective To assess the glycemic efficacy of DU 1.5 mg in patients with T2D when added on background of commonly used OAD regimens. Methods: Patients from 7 Phase-3 trials where DU 1.5 mg was added to OADs were pooled and categorized based on OAD regimens into the following categories; Metformin (MET), sulfonylurea (SU), MET + SU, MET + Pioglitazone, MET + SGLT2i. DU 0.75 mg was assessed in only 5 studies and hence not included in this analysis. Change from baseline in HbA1c, fasting serum glucose and body weight, % patients with HbA1c &amp;lt;7%, GI adverse events and hypoglycemia were assessed. Results: Table 1 summarizes the glycemic and weight outcomes of DU at baseline and after 6 months for different OAD categories. HbA1c reduction of -1.3 to -1.6% and weight change of -0.8 to -2.9 kg was seen when DU was added to different OADs. Nausea, vomiting and diarrhea were reported by 10-35%, 4-19% and 6-28% patients respectively. Severe hypoglycemia occurred in 1 patient in MET+SU group. Conclusion: In patients with T2D on different OAD regimens and requiring an additional glycemic control, DU demonstrated clinically meaningful glycemic control making it an effective first injectable option. Disclosure H. Patel: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. K.M. Munir: None. S.S. Sutherland: Other Relationship; Self; Eli Lilly and Company. M. Konig: Employee; Self; Eli Lilly and Company, Eli Lilly and Company.