Published online Nov 15, 2020. doi: 10.4239/wjd.v11.i11.540
Peer-review started: August 13, 2020
First decision: September 16, 2020
Revised: September 29, 2020
Accepted: October 19, 2020
Article in press: October 19, 2020
Published online: November 15, 2020
The sodium/glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like-1 receptor agonists (GLP-1RA) are antidiabetic agents effective both in hemoglobin A1c (HbA1c) reduction (with a low risk of hypoglycemia) and cardiovascular event prevention. In patients with type 2 diabetes, the add-on value of combination therapy of GLP-1RA and an SGLT-2i seems promising.
To investigate whether the efficacy of GLP-1RA and SGLT-2i combination observed in randomized controlled trials translates into therapeutic benefits in the Croatian population during routine clinical practice and follow-up.
We included 200 type 2 diabetes patients with poor glycemic control and analyzed the effects of treatment intensification with (1) GLP-1RA on top of SGLT-2i, (2) SGLT-2i on top of GLP-1RA compared to (3) simultaneous addition of both agents. The primary study endpoint was the proportion of participants with HbA1c < 7.0% and/or 5% bodyweight reduction. Secondary outcomes included changes in fasting plasma glucose (FPG), prandial plasma glucose, low-density lipoprotein cholesterol, estimated glomerular filtration rate (eGFR), and cardiovascular (CV) incidents assessment over a follow-up period of 12 mo.
The majority of patients were over 65-years-old, had diabetes duration for more than 10 years. The initial body mass index was 39.41 ± 5.49 kg/m2 and HbA1c 8.32 ± 1.26%. Around half of the patients in all three groups achieved target HbA1c below 7%. A more pronounced decrease in the HbA1c seen with simultaneous SGLT-2i and GLP-1RA therapy was a result of higher baseline HbA1c and not the effect of initiating combination therapy. The number of patients achieving FPG below 7.0 mmol/L was significantly higher in the SGLT-2i group (P = 0.021), and 5% weight loss was dominantly achieved in the simultaneous therapy group (P = 0.044). A composite outcome (reduction of HbA1c below 7% (53 mmol/mol) with 5% weight loss) was achieved in 32.3% of total patients included in the study. Only 18.2% of patients attained composite outcome defined as HbA1c below 7% (53 mmol/mol) with 5% weight loss and low-density lipoprotein cholesterol < 2.5 mmol/L. There were no significant differences between treatment groups. No differences were observed regarding CV incidents or eGFR according to treatment group over a follow-up period.
Combination therapy with GLP-1RA and SGLT-2i is effective in terms of metabolic control, although it remains to be determined whether simultaneous or sequential intensification is better.
Core Tip: Both glucagon-like-1 receptor agonists and sodium/glucose cotransporter-2 inhibitors when added sequentially to the other or simultaneously decrease the hemoglobin A1c (HbA1c) and reduce the body mass index, but the weight loss and glucose-lowering potential is not additive in case of their simultaneous use. Half of the patients achieved target HbA1c below 7%, irrespective of treatment group (sequential or simultaneous addition). Five percent weight loss was dominantly achieved in the simultaneous therapy group. Composite outcome (reduction of HbA1c below 7% with 5% weight loss) was achieved in 32.3%, while 18.2% of total patients attained composite outcome defined as HbA1c below 7% with 5% weight loss and low-density lipoprotein cholesterol < 2.5 mmol/L.