11 February 2016Fixed-dose combination of a sodium glucose co-transporter type 2 (SGLT-2) inhibitor plus dipeptidyl peptidase-4 (DPP4) inhibitor
GlyxambiType 2 diabetes mellitus
Development and Regulatory status
May 19Available in the UK. Price 1 x 28 film-coated tablet pack = £55.88, both strengths 
Jul 18EU positive opinion to expand the empagliflozin/ linagliptin licence to include positive effects on cardiovascular and renal outcomes .
Nov 16EMA granted marketing authorisation which is valid throughout the EU .
Sep 16EU positive opinion for use in adults with type 2 diabetes when metformin and/or sulphonylurea, and one of its monocomponents do not provide adequate glycaemic control, or when already being treated with free combination of empagliflozin and linagliptin .
Nov 15Filed in EU via centralised procedure .
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 .
May 15FDA safety warning after over 20 cases of diabetic ketoacidosis (DKA), requiring hospitalisation, were seen in pts treated with SGLT2 inhibitors to date. The FDA warned that pts taking SGLT2 inhibitors should monitor themselves for any signs of ketoacidosis, such as difficulty breathing, nausea, vomiting, abdominal pain, confusion, and unusual fatigue or sleepiness .
Mar 15Launched in the US. Glyxambi is the first treatment in the US to combine a sodium glucose co-transporter-2 inhibitor and a dipeptidyl peptidase-4 inhibitor .
Feb 15Approved in the US .
Apr 14Filed in the US for the treatment of T2DM .
Aug 11PIII study started .
Fixed-dose combination of a sodium glucose co-transporter type 2 (SGLT-2) inhibitor plus dipeptidyl peptidase-4 (DPP4) 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 .
Type 2 diabetes mellitus
Trial or other data
Feb 16The EMA has confirmed recommendations to minimise the risk of diabetic ketoacidosis in patients taking SGLT2 inhibitors (a class of type 2 diabetes medicines).
Oct 15PRAC recommendation based on safety review of SGLT2 inhibitors expected in Feb 16 .
Jun 15The PRAC of the EMA has started a review of the SGLT2 inhibitors) with the aim of evaluating their risk of diabetic ketoacidosis. It is estimated that the review will compete in Oct 15 .
Jan 15Results of a 52 week phase III study (n=686) have been published in Diabetes care. At week 24, the primary end point of change from baseline in HbA1c with empagliflozin/linagliptin were superior to those with empagliflozin or linagliptin alone as add-on to metformin (p<0.001 for all comparisons); efficacy was maintained at week 52. The proportion of adverse events was similar across treatment arms.
Jun 14Two 52-week PIII trials presented at the American Diabetes Association 74th Scientific Sessions. In one study (n=686) (mean baseline A1C of 8.0%), both empagliflozin/linagliptin combination doses showed statistically significant reductions in A1C vs. the empagliflozin component dose or linagliptin alone. Statistically significantly more adults who had A1C levels of 7.0% or more at baseline achieved A1C levels less than 7.0% after 24 weeks with both doses of the empagliflozin/linagliptin combination versus either empagliflozin or linagliptin alone. Empagliflozin 25 mg/linagliptin 5 mg 61.8%; empagliflozin 10 mg/linagliptin 5 mg 57.8%; empagliflozin 25 mg 32.6%; empagliflozin 10 mg 28.0%; linagliptin 5 mg 36.1%. For adults who had A1C levels of 8.5% or greater at baseline, empagliflozin 25 mg/linagliptin 5 mg combination reduced A1C by 1.8% vs. 1.2% for empagliflozin 25 mg. Epagliflozin 10 mg/linagliptin 5 mg combination reduced A1C by 1.6% vs. 1.3% for empagliflozin 10 mg. Linagliptin 5 mg alone reduced A1C by 1.0%. Empagliflozin/linagliptin combinations resulted in weight loss similar to that of empagliflozin monotherapy. Empagliflozin 25 mg/linagliptin 5 mg: body weight reduction of 3.0 kg from a mean baseline of 85.5 kg. Empagliflozin 10 mg/linagliptin 5 mg: body weight reduction of 2.6 kg from a mean baseline of 86.6 kg. Empagliflozin 25 mg: body weight reduction of 3.2 kg from a mean baseline of 87.7 kg. Empagliflozin 10 mg: body weight reduction of 2.5 kg from a mean baseline of 86.1 kg. In the second study (n=677) (mean A1C of 8.0% at baseline) A1C reduction with the empagliflozin 25 mg/linagliptin 5 mg combination was not statistically significantly greater than that of empagliflozin 25 mg. A1C reduction with the empagliflozin 10 mg/linagliptin 5 mg combination was significantly greater than that of empagliflozin 10 mg alone. Compared with linagliptin 5 mg, both combination doses significantly reduced A1C and body weight. Significantly more adults who had A1C levels of 7.0% or more at baseline achieved A1C levels less than 7.0% after 24 weeks with both doses of the empagliflozin/linagliptin combination versus the empagliflozin component dose or linagliptin alone. Empagliflozin 25 mg/linagliptin 5 mg 55.4%; empagliflozin 10 mg/linagliptin 5 mg 62.3%; empagliflozin 25 mg 41.5%; empagliflozin 10 mg 38.8%; linagliptin 5 mg 32.3% .
Mar 13PIII study started in December 2012 in patients with type-2 diabetes mellitus inadequately-controlled on once-daily linagliptin on a background of metformin(EudraCT2012-002270-31; NCT01734785). The fixed-dose combination, 10 or 25 mg empagliflozin with 5mg linagliptin once-daily, will be compared with linagliptin alone or placebo. 
Aug 11NCT01422876: a PIII randomized, double-blind, parallel group study of once daily oral of empagliflozin 25mg/ linagliptin 5mg and empagliflozin 10mg/ linagliptin 5mg fixed dose combination tablets vs the individual components for 52 weeks in 1300 treatment naïve and metformin treated patients with T2DM with insufficient glycaemic control (HbA1c between 7 to10.5%). The primary outcome is change from baseline in HbA1c at 24 weeks. The study will start Aug 11 and is due to complete Sep 13 .