Cardiovascular Safety of Saxagliptin In Patients With Type 2 Diabetes Mellitus: A Systematic Review And Meta-Analysis

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PDB18 Real World Tolerability And Effectiveness of Exenatide OnceWeekly Compared To Basal Insulin Among Elderly Patients with Type 2 Diabetes (T2D) Seeger JD1, Loughlin AM2, Qiao Q3, Nunes AP2, Ezzy S2, Yochum LA2, Clifford CR2, Gately R2, Ohman P4, Dore DD2 1and Assistant Professor, Division of Pharmacoepidemiology and Pharmacoeconomics, Harvard Medical School/Brigham and Women’s Hospital, Waltham, MA, USA, 2Optum, Waltham, MA, USA, 3Astrazeneca Phamaceuticals , LP, MoIndal, Sweden, 4Astrazeneca Phamaceuticals , LP, Gaithersburg, MD, USA

Objectives: To assess the tolerability and effectiveness of exenatide once-weekly (EQW) versus basal insulin (BI), among elderly T2D patients.  Methods: From a large US EHR database, we selected injectable-naïve T2D patients initiating EQW or BI between 2012 and 2015, into propensity score matched cohort study. We analyzed a subgroup of 1,447 T2D patients aged 65+ years. Weight and HbA1c were identified at baseline and quarterly in the first year, and were compared using interval means, absolute change from baseline and 95% confidence intervals (CI). We identified nausea and vomiting using diagnostic codes, and hypoglycemia using diagnostic codes and clinical notes. Incidence per 1,000 person-years, relative risk (RR) and 95% CI of each were used to compare risk in EQW relative to BI.  Results: Baseline characteristics were balanced in across comparators, [e.g., weight (kg), 65-74 years: 103.0 (EQW) and 101.6 (BI); 75+ years: 95.7 (EQW) and 92.8 (BI); HbA1c%: 65-74 years: 7.9 (EQW) and 8.0 (BI), 75+ years: 7.9 (EQW) and 7.6 (BI)]. In patients aged 65-74 years, EQW initiators lost 1.3 kg by Q2 increasing to 1.6 kg by year’s end, and weight did not change among BI initiators. Among patients 75+ years, EQW initiators lost more weight early, and by years end both groups lost weight (-1.98 kg (EQW), -1.45 kg (BI)). HbA1c% declined more among EQW initiators regardless of age (65-75 years: -0.5 (EQW), -0.34 (BI); 75+ years: - 0.5% (EQW), -0.14 (BI)). The hypoglycemia incidence was similar across comparators (65-74 years: RR= 0.91, 75+ years: RR= 0.97). Nausea and vomiting was more common among EQW versus BI in both age groups [65-74 years: RR=  1.77 (95% CI: 1.16, 2.69); 75+ years: RR= 1.32 (95% CI: 0.57, 3.04)].  Conclusions: Relative to BI, elderly EQW patients had more weight loss, improved HbA1c, and similar rates of hypoglycemia. However, nausea and vomiting risk was increased among EQW treated patients aged 65-74 years. PDB19 The Patient-Risk of Hypoglycaemia As A Function of Pharmacological Treatments. A Retrospective Analysis on Database Hypothesis Ravasio R1, Forlani G2, Veronese G2, Crocchiolo D3, Veneziano MA3, Marchesini G2 1Health Publishing & Services, Milano, Italy, 2Alma mater, University Bologna, Bologna, Italy, 3MSD Italy, Rome, Italy

Objectives: The analysis described the main characteristics of patients attending emergency departments (EDs) following an episode of hypoglycaemia. The analysis focused on pharmacological treatments and on the final outcome of hypoglycaemia.  Methods: A retrospective analysis (January-December 2011) on episodes of hypoglycaemia was carried out in 46 Italian EDs. According to a predefined case report form, the database (HYPOTHESIS), covering an area of approximately 12 million inhabitants, collected the demographic, clinical and pharmacological data of patients with diabetes requiring ED visits with an acceptance diagnosis of hypoglycaemia.  Results: A total of 1,922 episodes were retrieved in subjects with diabetes (mean age, 71.5 years [+16.8]; male 50.1%). Comorbidities were recorded in 1,380 (71.8%) episodes. Patients were treated with insulin alone (55.0%), insulin in combination with oral agents (15.3%), monotherapy oral agents (13.8%) and two or more oral agents (15.9%). The annual patient-risk for an episode of hypoglycaemia, estimated on the basis of the average Italian drug use, was higher in patients treated with insulin alone (1.27%) than treated with insulin in combination with oral agents (0.41%), or with monotherapy oral agents (0.10%) or with two or more oral agents (0.17%). Admission to hospital was necessary in 640 cases (33.3%). Monotherapy with sulphonylureas (SU) (OR, 1.14; 95%CI, 0.79-1.63), increasing age (OR, 1.03; 95% CI, 1.02-1.04) and the number of comorbidities (OR, 1.55; 95%CI, 1.40-1.71) were the main drivers of hospital admission. Considering SU monotherapy, or combination with insulin and/or other oral agents, the annual patient-risk of hypoglycaemia was 0.16% for patient treated with glimepiride, 0.12% with gliclazide, 0.20% with glibenclamide and 0.28% with repaglinide. Differences among SUs were not statistical significant.  Conclusions: Hypoglycaemia requiring referral to EDs is more frequently associated to a patient treated with insulin. Hypoglycaemia requiring a hospital admission is associated with age, comorbidities and SU monotherapy. PDB20 Cardiovascular Safety of Saxagliptin In Patients With Type 2 Diabetes Mellitus: A Systematic Review And Meta-Analysis Mothe RK, Ganji K, Esam H, Likhar N, Chidirala SR, Sharma A, Jain P, Sirumalla Y, Dang A MarksMan Healthcare Solutions LLP, Health Economics and Outcomes Research (HEOR) and RWE (Real World Evidence), Navi Mumbai, India

Objectives: To evaluate the association between saxagliptin and cardiovascular risk in patients with type 2 diabetes mellitus (T2DM).  Methods: Literature searches were performed in PubMed, CENTRAL, and ClinicalTrials.gov. In addition, reference lists of included studies were cross-checked for relevant studies. RCTs (≥ 24 weeks) that compared saxagliptin against placebo, or active antidiabetic drugs in adult patients (≥ 18 years) with T2DM, and reported cardiovascular outcomes were included.  Results: Of 26778 (19 trials) treated patients (mean±SD HbA1c 8.2±0.8%, age 56±10.11 years, BMI 30.2±4.9 kg/m2), 14649 received saxagliptin once daily and 12129 received comparators. There was no significant difference between saxagliptin 2.5mg and placebo on myocardial infarction (MI) [2.5mg: odds ratio (OR) 0.22, 95% confidence interval (CI) 0.04 to 1.31, 3 trials, n= 1083], cardiovascular mortality (OR 0.80, 95% CI 0.25 to 2.54, 2 trials, n= 886), acute MI (OR 0.46, 95% CI 0.10 to 2.05, 4 trials, n= 1239), congestive-heart failure (OR 0.23, 95% CI 0.03 to 2.09, 2 trials, n= 749)

and angina pectoris (OR 0.33, 95% CI 0.05 to 2.08, 4 trials, n= 1412) at week 24. Similar findings were observed on MI (OR 0.61, 95% CI 0.19, 1.96, 6 trials, n= 2762), cardiovascular mortality (OR 0.95, 95% CI 0.22, 4.17, 4 trials, n= 1287), acute MI (OR 0.51, 95% CI 0.19, 1.37, 7 trials, n= 2488), congestive-heart failure (OR 0.95, 95% CI 0.21, 4.22, 2 trials, n= 741) and angina pectoris (OR 0.70, 95% CI 0.20, 2.51, 6 trials, n= 2010) between saxagliptin 5mg and placebo at week 24. However, at week 24, the odds of heart failure with saxagliptin (5mg) was 1.8 times higher than placebo (OR 1.78, 95% CI 1.27 to 2.50, 4 trials, n= 17796).  Conclusions: Evidence suggests no increased risk of cardiovascular MI/mortality/congestive-heart failure/angina-pectoris with saxagliptin 2.5/5mg in T2DM patients. However, limited evidence suggests that saxagliptin 5mg is associated with increased risk of heart failure among T2DM patients.

DIABETES/ENDOCRINE DISORDERS – Cost Studies PDB21 Budget Impact Analysis of Lanreotide Autogel 120 Mg in the Treatment of Acromegaly in Poland Orlewska E1, Kos-Kudla B2, Sowinski J3, Sworczak K4, Zgliczynski W5 1Jan Kochanowski University, Kielce, Poland, 2Silesian Medical University, Katowice, Poland, 3Poznan University of Medical Sciences, Poznan, Poland, 4Medical University, Gdansk, Gdansk, Poland, 5Centre of Postgraduate Medical Education, Warsaw, Poland

Objectives: Long-acting somatostatin receptor ligands (SRLs) approved as depot formulations are administered monthly, with an approved extension of a 6- 8 week subcutaneous injection interval possible for lanreotide (ATG120). Polish prospective non-interventional 2-years Lanro-Study showed that 48% patients received ATG120 mg at an extended duration interval. The aim of this study was to estimate the financial consequences of increasing the use of ATG120 in the treatment of acromegaly in Poland.  Methods: An Excel-based budget impact model was developed to estimate the annual costs associated with treatment of acromegalic patients from the perspective of public payer in 2-years time horizon, using Polish epidemiologic and sales data, Lanro-Study results and drug acquisition costs. The following scenarios were compared: 1) current intervention mix (different dosage regimens of SRLs); 2) ATG120 is the 1-line medical treatment for all new patients; 3) all new and 50% of patients using so far octreotide LAR are treated with ATG120. in scenario 2) and 3) inadequately controlled patients were switched to octreotide after 6 months. Results were expressed in PLN (1 EURO= 4.2 PLN in 2015). Scenario sensitivity analyses were performed  Results: In the scenario 1) the public payer expenditure on SRLs were estimated to be 47 997 242 PLN in 1st. and 51 596 170 PLN in 2nd year. Increasing the use of ATG120 is expected to reduce costs in 2 consecutive years by 212 478 PLN and 637 433 PLN in scenario 2), and 4 624 367 PLN and 5 049 322 PLN in scenario 3). Scenario analysis confirmed that savings were associated with the number of patients treated with ATG120 at an extended duration interval.  Conclusions: The results indicate that by increasing the use of ATG120 in the management of acromegaly, cost savings for the Polish health care system are anticipated. PDB22 Impact of Empagliflozin (Jardiance) to the NHS: Estimation of Budget and Event Impact Based on Empa-Reg Outcome Data Daacke I1, Kandaswamy P2, Tebboth A3, Kansal A4, Reifsnider O4 1Boehringer Ingelheim, Bracknell, UK, 2Boehringer Ingelheim GmbH, Ingelheim, Germany, 3Boehringer Ingelheim UK, Bracknell, UK, 4Evidera, Bethesda, MD, USA

Objectives: The EMPA-REG OUTCOME trial was a randomized, double-blind, placebo-controlled, cardiovascular (CV) safety trial which examined the longterm effects of empagliflozin versus placebo, in addition to standard of care, on CV morbidity and mortality in patients with T2DM and a high risk of CV events. Empagliflozin showed 38% reduction in CV death (95% CI: 0.49-0.77, p< 0.001) and a 35% reduction in hospitalisation for heart failure (95% CI: 0.50-0.85, p= 0.002). A posthoc analysis showed a 39% reduction in nephropathy (95% CI: 0.53-0.70, p< 0.001) and a 55% reduction in renal replacement therapy (95% CI: 0.21-0.97, p= 0.04). The objective was to quantify the financial and clinical event impact of empagliflozin for treatment of patients with T2DM at increased CV risk based on the EMPA-REG OUTCOME™ study.  Methods: A budget impact economic model was created to compare the impact of the addition of empagliflozin to standard of care. Drug use was estimated based on the drug use seen in EMPA-REG OUTCOME. Event rates were based on the event rates seen in EMPA-REG OUTCOME and event costs were based on NHS tariff costs. The model determines the incremental budget impact and potential number of events saved for empagliflozin versus usual care for treatment in high-risk patients with T2DM.  Results: Taking the total number of patients on the quality outcomes framework registry, it is estimated that 194,233 patients would be eligible to have empagliflozin added to their treatment regime. Over 3 years, this could result in 2,719 heart failures avoided and 5,050 lives saved with empagliflozin. An estimated £19,492,057 could be saved by the NHS budget due to the reduction in A&E admissions.  Conclusions: Cost savings could be realized when treating high CV risk diabetes patients with empagliflozin. Multiple adverse events could also be avoided, providing better outcomes to patients. PDB23 Budget Impact Estimation of Changes In Reimbursement of Basal Insulin Therapies in Hungary Andriska P1, Tarcsa M2, Bán A2, Nagy B1 1Healthware Consulting Ltd., Budapest, Hungary, 2Sanofi-Aventis Magyarország Kereskedelmi és Szolgáltató Zártkörűen Működő Részvénytársaság, Budapest, Hungary

Objectives: Numerous studies presented that the direct drug and cost of hypoglycemic episodes (hypo) have a significant impact on the burden of diabetes mellitus. It is also evidenced that analogues have a more favorable hypo pattern although imply higher direct drug costs. The aim of the study is to demonstrate intervention