Linagliptin

ArticlesMedicine Compliance Aid StabilityLactation Safety InformationNew Medicines ·
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Articles

Medicine Compliance Aid Stability

TrajentaBoehringer Ingelheim

Boehringer Ingelheim
Trajenta
Tablets 5mg
G1 · Green 1Stability data indicates that the drug is suitable for CAs and there are no theoretical concerns with the product.
No special precautions for storage
No special precautions for storage
21 January 2015

Lactation Safety Information

Insulin, metformin or alternative approropriate antidiabetic drug
Minimal absorption from the infant's GI tract
No published evidence of safety
Infant hypoglycaemia would not be expected due to its mechanism of action
22 September 2020

New Medicines

Trajenta [EU]; Tradjenta [US]Type 2 diabetes mellitus; with renal disease

Information

Trajenta [EU]; Tradjenta [US]
Licence extension / variation
Boehringer Ingelheim
Eli Lilly

Development and Regulatory status

Launched
Launched
Phase III Clinical Trials
March 2019
Mar 19Linagliptin SPC updated with cardiovascular and renal safety data from the CARMELINA study but no change made to the licence. Boehringer-Ingelheim will not be pursuing any further changes or updates to the licence based on this study [9,10]
Dec 18Listed in Boehringer-ingelheim pipeline as PIII for T2D with renal disease [7].
Sep 15The US FDA warns that sitagliptin, saxagliptin, linagliptin, and alogliptin may cause joint pain that can be severe and disabling. The US FDA has added a new Warning and Precaution about this risk to the labels of all medicines for all dipeptidyl peptidase-4 (DPP-4) inhibitors [5].
Apr 15Listed in Boehringer-ingelheim pipeline as PIII for type 2 diabetes with renal disease [4].

Category

Dipeptidylpeptidase-4 (DPP-4) inhibitor
Currently 3.8 million people in the UK are diagnosed with diabetes (90% type 2), and it is estimated that a further 1 million people with type 2 diabetes have not yet been diagnosed [8].
Type 2 diabetes mellitus; with renal disease
Oral

Trial or other data

Aug 19Exploratory substudy of CARMELINA reported that linagliptin did not modulate cognitive decline versus placebo over 2.5 years (n= 1,545; accelerated cognitive decline occurred in 28.4% vs. 29.3%, respectively; OR, 0.96; 95% CI 0.77, 1.19) [12].
Jul 18Boehringer Ingelheim announces that treatment with linagliptin met its primary endpoint of time to first occurrence of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke (3-point MACE) assessed at 54 months, in the CARMELINA [CArdiovascular safety and Renal Microvascular outcomE with LINAgliptin] phase IV trial that evaluated the efficacy and safety of linagliptin in patients with type 2 diabetes mellitus (NCT01897532). The trial enrolled 6,979 adult patients in 27 countries. Cardiovascular safety of linagliptin was comparable with placebo in the trial [11].
Jun 16Boehringer Ingelheim release positive efficacy and safety data from PIII MARLINA trial (n=360). At week 24, treatment with linagliptin led to a significant 0.6% reduction in HbA1C vs placebo. Change in albuminuria, was non-significant, when measured by UACR [6].
Jan 15Results of a double-blind RCT of linagliptin in patients with renal impairment published in Diabetes Care. The trial comprised a 12-week, placebo-controlled phase followed by a 40-week, active-controlled extension. Patients (n=235) with T2DM and severe renal impairment (eGFR <60 mL/min/1.73 m2) were randomized to linagliptin 5 mg/day or placebo for 12 weeks; placebo patients were then switched to glimepiride 1–4 mg/day, and treatments continued until week 52. After 12 weeks, change from baseline in HbA1c was –0.53% with linagliptin vs. –0.11% with placebo (p<0.0001). At 52 weeks the figures were –0.64% liraglutide and –0.50% with glimepiride. [3]
Mar 14The MARLINA (NCT01792518) trial continues to recruit pts; it is now expected to complete Feb 15 [2].
Mar 13A PIIIb trial (MARLINA, NCT01792518) has started to evaluate glycaemic efficacy and safety of linagliptin in 404 patienrts with T2DM with micro- or macroalbuminuria (30-3000mg/g creatinine), in addition to current standard therapy for diabetic nephropathy (ACEi or ARB). The primary endpoint is the change from baseline in HbA1c after 24 weeks of treatment. The study is expected to complete Jul 2014 [1]

Evidence based evaluations

Trajenta [EU]; Tradjenta [US]Cardiovascular disease - prevention of CV events in patients with type 2 diabetes mellitus

Information

Trajenta [EU]; Tradjenta [US]
Licence extension / variation
Boehringer Ingelheim
Eli Lilly

Development and Regulatory status

Launched
Launched
Pre-registration (Filed)
March 2019
Mar 19Linagliptin SPC updated with cardiovascular and renal safety data from the CARMELINA study but no change made to the licence. Boehringer-Ingelheim will not be pursuing any further changes or updates to the licence based on this study [7,8].
Sep 18Eli Lilly files sNDA for inclusion of data from CARMELINA trial to the label of linagliptin treatment of patients with T2DM in the US [2].

Category

Dipeptidylpeptidase-4 (DPP-4) inhibitor
Currently 3.8 million people in the UK are diagnosed with diabetes (90% type 2), and it is estimated that a further 1 million people with type 2 diabetes have not yet been diagnosed [5]. People with diabetes account for one quarter to one third of hospital admissions for cardiovascular disease [6].
Cardiovascular disease - prevention of CV events in patients with type 2 diabetes mellitus
Oral

Trial or other data

Jun 19Results from the multi-national, randomised, double-blind, active-controlled PIII CAROLINA trial (NCT01243424; n=6033) reported at the American Diabetes Association´s 79th Scientific Sessions demonstrated linagliptin did not increase cardiovascular risk compared with glimepiride in adults with type 2 diabetes and cardiovascular risk. The trial met its primary endpoint, defined as non-inferiority for linagliptin vs glimepiride in time to first occurrence of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke (3P-MACE), which occurred in 11.8% (n=356) of the linagliptin group vs 12% (n=362) of the glimepiride group. Lilly and Boehringer suggest that the findings from CAROLINA complement the results from CARMELINA [9] .
Nov 18CARMELEINA published in JAMA. Linagliptin added to usual care vs placebo added to usual care resulted in a non-inferior risk of CV outcome (CV death, non-fatal MI or nonfatal stroke) over median 2.2 years (12.4% vs 12.1%; HR, 1.02; p<0.001 for non-inferiority) [3].
Nov 18Secondary analysis of CARMELINA (published in Circulation) found that linagliptin did not affect the risk of hospitalisation for HF or other selected HF-related outcomes, including among participants with /without history of HF, across spectrum of kidney disease, and independent of previous LVEF [4].
Jul 18Boehringer Ingelheim announces that treatment with linagliptin met its primary endpoint of time to first occurrence of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke (3-point MACE) assessed at 54 months, in the CARMELINA [CArdiovascular safety and Renal Microvascular outcomE with LINAgliptin] phase IV trial that evaluated the efficacy and safety of linagliptin in patients with type 2 diabetes mellitus (NCT01897532). The trial enrolled 6,979 adult patients in 27 countries. Cardiovascular safety of linagliptin was comparable with placebo in the trial [2].