Addition of Ozempic to a SGLT2 inhibitor improves hyperglycemia and bodyweight

Clinical experience has consistently shown that addition of a GLP-1 agonist to a SGLT2 inhibitor improves hyperglycemia in patients with uncontrolled diabetes. Current study SUSTAIN 9 proves just that for semaglutide, a once weekly injectable GLP-1 agonist.

Addition of semaglutide reduced A1c by 1.4% and bodyweight by 8.4 lbs. Results were statistically significant. As expected, the GI side effects were more pronounced with semaglutide. About 72% of patients were also taking metformin and 13% sulfonylurea.

A group of 300 participants were followed for 30 weeks.


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GLP1 agonist

SGLT2 inhibitors

Diabetes posts

Lancet, Diabetes and Endocrinology


March 2019



Semaglutide is a once-weekly glucagon-like peptide-1 (GLP-1) analogue for DM2 (DM2). Few clinical trials have reported on the concomitant use of GLP-1 receptor agonists with sodium-glucose cotransporter-2 (SGLT-2) inhibitors. We aimed to investigate the efficacy and safety of semaglutide when added to SGLT-2 inhibitor therapy in patients with inadequately controlled DM2.



The SUSTAIN 9 double-blind, parallel-group trial was done at 61 centers in six countries (Austria, Canada, Japan, Norway, Russia, and the USA).

Adults with DM2 and A1c 7.0–10%, despite at least 90 days of treatment with an SGLT-2 inhibitor, were randomly assigned (1:1) to receive subcutaneous semaglutide 1.0 mg or volume-matched placebo once weekly for 30 weeks, after a dose-escalation schedule of 4 weeks of 0.25 mg semaglutide or placebo and 4 weeks of 0.5 mg semaglutide or placebo.

Existing antidiabetic medications, including SGLT-2 inhibitor treatment, were continued for the duration of the trial. Rescue medication, defined as intensification of background antidiabetic treatment or the initiation of new glucose-lowering medications, could be given to patients meeting specific criteria at the discretion of the investigator.

  • The primary outcome was change in A1c from baseline at week 30, assessed in the full analysis set (all patients randomly allocated to treatment) using on-treatment data collected before rescue medication was started.

  • The confirmatory secondary outcome was change in body-weight from baseline to week 30.

Safety was also assessed in the safety analysis set (all patients who received at least one dose of treatment).



Between 3/15 and 12/2017, 302 patients were enrolled and randomly assigned to receive semaglutide 1.0 mg or placebo (full analysis set), of whom 301 received at least one dose of treatment (safety analysis set). One patient was assigned to semaglutide but was not treated (reason unknown). 294 (97.4%) patients completed the trial and 267 (88.4%) completed treatment.

Baseline characteristics were generally comparable between groups. In addition to randomized medication and SGLT-2 inhibitor, 216 (71.5%) patients were taking metformin, and 39 (12.9%) were taking sulphonylurea.

  • Patients given semaglutide had greater reductions in A1c (estimated treatment difference −1.42% and bodyweight −8.4 lbs those randomized to placebo (both p<0.0001).

356 adverse events were reported by 104 (69.3%) patients in the semaglutide group, and 247 adverse events were reported by 91 (60.3%) patients in the placebo group.

Gastrointestinal adverse events were most common and were reported in 56 (37.3%) patients in the semaglutide group and 20 (13.2%) in the placebo group.

Serious adverse events occurred in seven (4.7%) patients in the semaglutide group and six (4.0%) in the placebo group. Severe or blood glucose-confirmed hypoglycaemic events were reported in four patients on semaglutide (2.7%). 16 patients stopped treatment early because of an adverse event, 13 of whom were in the semaglutide group. There were no deaths during the trial.



Adding semaglutide to SGLT-2 inhibitor therapy significantly improves glycemic control and reduces body-weight in patients with inadequately controlled DM2 and is generally well tolerated.

Semaglutide Pens