Janumet XR (sitagliptin/metformin extended-release) / Merck (MSD), PDL - LARVOL DELTA

Emerging Trends in List Price Adjustment Strategies Following Implementation of the Inflation Reduction Act (ISPOR 2025) - "Among products analyzed, Pfizer's Atgam experienced the largest price increase at +15%. In contrast, significant price decreases were observed for Boehringer Ingelheim's Atrovent (-35%) and Merck's Januvia and Janumet/Janumet XR (-42.4%)...Excluding Januvia, the year-over-year (YoY) percent change in price for the six other IRA negotiation products with 2025 data declined from +4.0% in 2024 to +2.4% in 2025; Eliquis had the largest shift YoY from +6% in 2024 to +2% in 2025. List price adjustments reflect both product-specific and broader industry dynamics... List price adjustments reflect both product-specific and broader industry dynamics. In anticipation of IRA negotiations, IRA products are experiencing lower than average price increases. As government regulations evolve and pricing pressure on pharmaceuticals increase, assessing price adjustments in the context of anticipated payer management and government penalties will be a key consideration for..."

Pharmacokinetic comparison of sitagliptin and metformin HCl extended-release tablets versus JANUMET XR in healthy volunteers under fasting and fed conditions. (PubMed, Front Pharmacol) - "The 90% CIs of C, AUC, and AUC in both studies were all within acceptance limits (80.00%-125.00%). The results demonstrated for the first time that sitagliptin 100 mg and metformin 1000 mg produced by Nanjing Chia-Tai Tianqing Pharmaceutical Company was bioequivalent to the branded Janumet XR, and both drugs were well tolerated."

Journal • PK/PD data • Diabetes • Metabolic Disorders

[VIRTUAL] Incidence of diabetic patients with ASCVD or Heart Failure on DPP4s and candidates for GLP-1 agonists or SGLT-2s for improved cardiovascular outcomes and reduced cost (ASHP 2020) - " Retrospective EMR Review (EPIC) Population: Patients with Type 2 Diabetes Mellitus with additional comorbidities of ASCVD or HF currently on therapy of DPP4 inhibitor Inclusion Criteria: Patients ≥ 18 years of age Patients with uncontrolled Type 2 Diabetes Mellitus + ASCVD or HF Patients on therapy of DPP4 Inhibitor Exclusion Criteria (based on chart review): Pregnancy Previous Failure of GLP-1 in patients with ASCVD Previous Failure of SGLT-2 inhibitors in patients with heart failure Patients on hemodialysis or continuous renal replacement therapy (CRRT) Patients with eGFR < 30 mL/min in patients with heart failure Patients with significant history of urinary tract infections (3+/year) in patients with heart failure History of pancreatitis in patients with ASCVD History of medullary thyroid carcinoma (MTC) in patients with ASCVD Patients with multiple endocrine neoplasia syndrome type 2 (MEN2) in patients with ASCVD Data Collection: Patient Demographics: Sex Age..."

Clinical • Allergy • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Immunology • Infectious Disease • Metabolic Disorders • Nephrology • Oncology • Pancreatitis • Renal Disease • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • Type 2 Diabetes Mellitus

[VIRTUAL] Utilization of sodium-glucose co-transporter-2 inhibitor as monotherapy in metformin intolerant patients (ASHP 2020) - "One study compared empagliflozin monotherapy to sitagliptin and placebo in treatment naïve type 2 diabetes patients...Other studies evaluated along with this case suggested safety and efficacy of empagliflozin and other SGLT2 inhibitors such as canagliflozin and dapagliflozin...It is also important to compare SGLT2 inhibitors to other agents for possibility of selecting a better agent in this particular group of patients. Although further studies are necessary to adapt this to common practice, providers can consider SGLT2 inhibitors as an initial treatment option in metformin intolerant patients."

Clinical • Monotherapy • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Diabetes • Dyslipidemia • Fibrosis • Gastrointestinal Disorder • Heart Failure • Hepatology • Hypertension • Immunology • Metabolic Disorders • Type 2 Diabetes Mellitus

[VIRTUAL] Cost-Effectiveness of Dipeptidylpeptidase-4 Inhibitors Added to Metformin in Patients with Type 2 Diabetes in China (ISPOR-EU 2020) - "OBJECTIVES : Agents that inhibit the dipeptidylpeptidase-4 (DPP-4) enzyme, including linagliptin, alogliptin, saxagliptin, sitagliptin and vildagliptin, become available for the treatment of Chinese patients with type 2 diabetes mellitus (T2DM)...Sensitivity analyses showed that the most influential parameters were the cost of DPP-4 inhibitors and their treatment efficacy. CONCLUSIONS : These results suggested that alogliptin was a preferred treatment option compared with other DPP-4 inhibitors for Chinese patients with T2DM inadequately controlled on metformin monotherapy."

Clinical • HEOR • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

A Pooled Analysis of the Safety and Efficacy of MK-0431A and MK-0431A XR in Pediatric Participants With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Therapy (Alone or in Combination With Insulin) (MK-0431A-170/MK-0431A-289) (clinicaltrials.gov) - P3; N=223; Completed; Sponsor: Merck Sharp & Dohme Corp.; N=101 ➔ 223

Combination therapy • Enrollment change • Diabetes • Metabolic Disorders • Pediatrics • Type 2 Diabetes Mellitus

A Study to Assess the Pharmacokinetics and Ability for Pediatric Patients with Type 2 Diabetes to Swallow MK-0431A XR Tablets (clinicaltrialsregister.eu) - P1; N=25; Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Clinical • New P1 trial • Diabetes • Metabolic Disorders • Pediatrics • Type 2 Diabetes Mellitus

Efficacy and safety with exenatide once weekly: clinical trial results from 10 randomised trials (the DURATION programme) (EASD 2018) - "...The DURATION-1 study was extended to 7 years of follow-up; currently, this is the longest duration that any GLP-1RA has been studied in a clinical trial.Materials and Patients received ExQWS-AI or ExQW as monotherapy or in combination with other antidiabetic drugs (e.g. metformin, sulphonylurea, a thiazolidinedione [pioglitazone], dapagliflozin [DAPA] and insulin glargine). Efficacy and safety data were summarised from individual studies. In total, 2251 patients received ExQW 2 mg (n=1841) or ExQWS-AI 2 mg (n=410); 2870 patients received comparators (non-GLP-1RAs, n=1481 [metformin, sitagliptin, pioglitazone, insulin glargine, and DAPA], ExBID [n=416], liraglutide [n=450], ExQW+DAPA [n=231], or placebo [n=292])... The 10 studies show consistent efficacy for ExQW (8 studies) and ExQWS-AI (2 studies) with HbA1c reductions of 1.0−1.9% at 24-30 weeks in patients with T2D with no new or unexpected safety findings in the integrated population. Consistent results were..."

Clinical • Biosimilar • Diabetes

Pharmacokinetic Characteristics of GLH1SM Extended Release Tablets in Healthy Volunteers(Fed) (clinicaltrials.gov) - P1; N=25; Completed; Sponsor: GL Pharm Tech Corporation; Enrolling by invitation ➔ Completed

Clinical • Trial completion

A Study of the Safety and Efficacy of MK-0431A XR in Pediatric Participants With Type 2 Diabetes Mellitus (MK-0431A-289) (clinicaltrials.gov) - P3; N=90; Recruiting; Sponsor: Merck Sharp & Dohme Corp.; Trial primary completion date: Jan 2016 ->Sep 2016

Trial primary completion date • Biosimilar • Diabetes

A study to evaluate the efficacy and safety of sitagliptin and MK0431A in comparison to a commonly used medication in patients with type 2 diabetes (clinicaltrials.gov) -

Diabetes

Mexico's Type 2 Diabetes Market Will Exceed $1.2 Billion In 2014 (PRNewswire) -

Type 2 diabetes market in Mexico will grow to $1.22B in 2014; Fixed-dose combination therapies constitute the largest drug-class sales with $289M  in sales in 2009 and $332M expected in 2014; This is due to the uptake of new combinations, such as Janumet and metformin plus pioglitazone (Rimsa's Diabamet and Eli Lilly's Competact);

Decision resources report

A Study to Assess the Pharmacokinetics and the Ability for Pediatric Participants With Type 2 Diabetes to Swallow MK-0431A XR Tablets (MK-0431A-296) (clinicaltrials.gov) - P1; N=24; Completed; Sponsor: Merck Sharp & Dohme Corp.; Trial primary completion date: Sep 2014 ->Apr 2014

Trial primary completion date • Biosimilar • Diabetes • Immunology • Myositis

A Study to Assess the Pharmacokinetics and the Ability for Pediatric Participants With Type 2 Diabetes to Swallow MK-0431A XR Tablets (MK-0431A-296) (clinicaltrials.gov) - P1; N=24; Completed; Sponsor: Merck Sharp & Dohme Corp.; N=36 -> 24

Enrollment change • Biosimilar • Diabetes • Immunology • Myositis

Merck: Annual Report 2013 (Merck (MSD)) - Anticipated compound patent expiry in US in 2022; Anticipated patent expiry on salt in US in 2026

Anticipated patent expiry • Diabetes

FDA approves Janumet XR (sitagliptin and metformin HCl extended-release) for type 2 diabetes, offering the powerful efficacy of Janumet (sitagliptin/metformin HCl) now available with once-daily convenience (Merck (MSD)) - Merck announced that the US FDA has approved its Janumet XR tablets as a new treatment for type 2 diabetes; The approval for Janumet XR was based upon a double-blind, placebo-controlled study of 1,091 pts who did not respond adequately to diet and exercise

FDA approval • Diabetes

PDL BioPharma: Q3 2013 Results (PDL BioPharma) - Anticipated approval in EU for type 2 diabetes in Q4 2016

Anticipated EU regulatory • Diabetes

A Study of the Safety and Efficacy of MK-0431A XR in Pediatric Participants With Type 2 Diabetes Mellitus (MK-0431A-289) (clinicaltrials.gov) - P3; N=101; Completed; Sponsor: Merck Sharp & Dohme Corp.; Active, not recruiting ➔ Completed

Clinical • Combination therapy • Trial completion

Pharmacokinetic Characteristics of GLH1SM Extended Release Tablets in Healthy Volunteers(Fed) (clinicaltrials.gov) - P1; N=30; Enrolling by invitation; Sponsor: GL Pharm Tech Corporation; Trial completion date: May 2019 ➔ Oct 2019; Trial primary completion date: May 2019 ➔ Sep 2019

Clinical • Trial completion date • Trial primary completion date

Semaglutide: Review and Place in Therapy for Adults With Type 2 Diabetes. (PubMed, Can J Diabetes) - "...Semaglutide, a recently approved glucagon-like peptide-1 receptor agonist, is indicated in Canada for adults with type 2 diabetes to improve glycemic control as monotherapy with diet and exercise when metformin is inappropriate or as an add-on to either metformin alone or metformin plus a sulfonylurea or basal insulin...Results from the completed trials support the superiority of semaglutide for reduction of glycated hemoglobin levels and weight loss vs. placebo as well as active comparators, including sitagliptin, exenatide extended-release, dulaglutide and insulin glargine...This article overviews data from across the semaglutide clinical trial program, including efficacy and safety results and findings from post hoc analyses. The potential place of semaglutide in clinical practice is discussed."

Clinical • Journal • Review

Evolution of the Designs of the Sitagliptin (SITA) Pediatric Clinical Studies (ADA 2019) - "Approved antihyperglycemic therapies for pediatric patients with T2D are currently limited to metformin (MET) and insulin. SITA is being evaluated in 3 studies in patients 10-17 years of age with T2D: SITA as initial oral therapy, MK-0431 P083; SITA as add-on to MET administered as a fixed dose combination (FDC), MK-0431A P170; and SITA as add-on to MET extended-release administered as a FDC of SITA and MET XR, MK-0431A XR P289...Of patients randomized after approval of an amendment that broadened the A1C entry criterion (from lower limit of 7.0% to 6.5%), ~34% in P083, ~20% in P170 and ~20% in P289 had a baseline A1C between 6.5% and 6.9%. Of patients randomized after approval of an amendment to include patients on background insulin, 11% of patients in P083, 22% in P170, and 19% in P289 enrolled on background insulin."

Clinical

Pharmacokinetic Characteristics of GLH1SM Extended Release Tablets in Healthy Volunteers(Fed) (clinicaltrials.gov) - P1; N=30; Enrolling by invitation; Sponsor: GL Pharm Tech Corporation; Not yet recruiting ➔ Enrolling by invitation

Clinical • Enrollment open

BUDGET IMPACT ANALYSIS OF SAXAGLIPTIN/METFORMIN EXTENDED-RELEASE TABLETS FOR THE TREATMENT OF PATIENTS WITH TYPE 2 DIABETES MELLITUS IN CHINA (ISPOR 2019) - "...The model assumed that the market share of target drug would increase with a consequent decrease of open dual therapies composed of metformin and DPP-4 inhibitors (saxagliptin, sitagliptin, vildagliptin, linagliptin, alogliptin), or metformin and alpha-glucosidase inhibitors (acarbose)...The budget impact was estimated to be -$2.69, -$6.92, -$17.49, -$32.22 and -$56.52 million, with adoption of target drug in NRDL. CONCLUSIONS : Adoption of saxagliptin/metformin extended-release tablets in NRDL would cause budget savings on Chinese health insurance expenditure in the long-term period, mainly driven by the lower price of fixed-dose combination drugs compared with open dual therapies."

Clinical • HEOR

Pharmacokinetic Characteristics of GLH1SM Extended Release Tablets in Healthy Volunteers(Fed) (clinicaltrials.gov) - P1; N=30; Not yet recruiting; Sponsor: GL Pharm Tech Corporation

New P1 trial

Pharmacokinetic Characteristics of GLH1SM Extended Release Tablets in Healthy Volunteers (clinicaltrials.gov) - P1; N=30; Completed; Sponsor: GL Pharm Tech Corporation; Enrolling by invitation ➔ Completed; Trial completion date: Apr 2019 ➔ Jan 2019

Clinical • Trial completion • Trial completion date