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Durable treatment response seen with dapagliflozin-saxagliptin add-on in T2D patients on metformin

Audrey Abella
25 Nov 2020

Reductions in liver fat and adipose tissue volumes were sustained in patients with type 2 diabetes (T2D) with the addition of the SGLT-2* inhibitor dapagliflozin (DAPA) and the DPP-4** inhibitor saxagliptin (SAXA) to metformin (MET), compared with a regimen comprising glimepiride (GLIM)+MET, according to the extension period results of a phase IIIb trial.

“[The] improvements in liver fat and adipose tissue volumes [observed at week 52] were maintained over a 122-week period during treatment with a fixed-dose combination of DAPA+SAXA+MET vs GLIM+MET,” said Dr Lars Johansson from Antaros Medical AB, Mölndal, Sweden, who presented the findings at AASLD 2020. The safety and tolerability profile of DAPA+SAXA+MET over 156 weeks was also consistent with the established profiles of the individual components, he added.

The initial study population comprised 444 participants who were randomized 1:1 to receive dapagliflozin 10 mg and saxagliptin 5 mg, or glimepiride 1–6 mg (12-week up-titration), on top of metformin. Each component was administered once-daily orally. In the 52-week analyses of this cohort, DAPA+SAXA+MET led to improvements in glycaemic control and reductions in liver fat and adipose tissue volumes compared with GLIM+MET. [Diabetes Obes Metab 2020;22:1083-1093; Diabetes Obes Metab 2020;22:1094-1101]

The current sub-study was conducted using MRI-PDFF*** to determine the long-term effects of DAPA+SAXA+MET on total liver fat content and visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) volumes. “[A]ssessing the effect of treatment on liver fat in addition to glycaemic control is of significant interest, [as] T2D is a risk factor for nonalcoholic fatty liver disease,” said Johansson.

Of the 338 participants who completed the 104-week extension phase, 82 consented to participate in the MRI sub-study. Of these, 46 patients were receiving DAPA+SAXA+MET (mean age 58.9 years, 47.8 percent female) while 36 were on GLIM+MET (mean age 56.9 years, 52.8 percent female). MRI outcomes were evaluated at week 122. [AASLD 2020, abstract 1719]

Week 122 saw significantly greater reductions in liver fat percentage (adjusted mean change, –4.49 percent vs 0.4 percent; pnominal<0.001) and adipose tissue volumes (adjusted mean change, –0.35 vs 0.06 L; pnominal=0.003 [VAT] and –0.43 vs 0.01 L; pnominal=0.008 [SAT]) with DAPA+SAXA+MET vs GLIM+MET. These also correlated with the week 52 MRI results.

These findings translate to relative mean reductions in liver fat by 32 percent, 10-percent reduction in VAT volume, and a 9-percent drop in SAT volume, noted Johansson.

These reductions were accompanied by greater mean reductions in total body weight (adjusted mean change, –4.36 vs 1.96 kg; pnominal<0.001) and HbA1c (adjusted mean change, –1.1 percent vs –0.73 percent; pnominal=0.241) in favour of DAPA+SAXA+MET over GLIM+MET through 156 weeks.

Both arms had consistent mean baseline Fibrosis-4 scores of <1.45 throughout 156 weeks which, as per Johansson, signifies the absence of advanced fibrosis.

DAPA+SAXA+MET also resulted in greater mean reduction in ALT# serum levels compared with GLIM+MET. The corresponding mean reduction in AST## serum levels was slightly greater with GLIM+MET vs DAPA+SAXA+MET, noted Johansson.

“[Taken together,] these data provide evidence on the long-term durability of treatment response [with DAPA+SAXA+MET] in patients with T2D,” said Johansson. “[I]n addition to reducing liver fat and associated markers of liver inflammation, DAPA+SAXA+MET also improves metabolic control.”

 

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Most Read Articles
10 Jan 2021
Regular practice of yoga postures confers benefits for glucose control, oxidative stress, inflammatory response, and sleep quality in patients with type 2 diabetes, a study has found.
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Dr. Hsu Li Yang, Dr. Tan Thuan Tong, Dr. Andrea Kwa, 08 Jan 2021
Antimicrobial resistance has become increasingly dire as the rapid emergence of drug resistance, especially gram-negative pathogens, has outpaced the development of new antibiotics. At a recent virtual symposium, Dr Hsu Li Yang, Vice Dean (Global Health) and Programme Leader (Infectious Diseases), NUS Saw Swee Hock School of Public Health, presented epidemiological data on multidrug-resistant (MDR) gram-negative bacteria (GNB) in Asia, while Dr Tan Thuan Tong, Head and Senior Consultant, Department of Infectious Diseases, Singapore General Hospital (SGH), focused on the role of ceftazidime-avibactam in MDR GNB infections. Dr Andrea Kwa, Assistant Director of Research, Department of Pharmacy, SGH, joined the panel in an interactive fireside chat, to discuss challenges, practical considerations, and solutions in MDR gram-negative infections. This Pfizer-sponsored symposium was chaired by Dr Ng Shin Yi, Head and Senior Consultant of Surgical Intensive Care, SGH.
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