Methabolic changes
HbA1c was significantly reduced by −1.4% at 12M and this reduction was maintained at 24 and 36M in the dulaglutide group (p<0.001). Similarly, fasting blood glucose levels showed significant reductions (−30 mg/dL) at 12M (p=0.005) and this reduction was also maintained until 24 and 36M follow-up. Weight showed a trend comparable to glucose levels. In the first 12M, the reduction was 3.6 kg (p=0.009), which remained unchanged at 36M (Table 2).
DiscussionOur results show for the first time, based on a real-life long-term follow-up study, that dulaglutide is an effective and nephroprotective drug for the treatment of patients with T2DM. It also allows an excellent metabolic control.
Despite optimal lifestyles, blood glucose, and hypertension management and/or the use of modular RAAS pathway drugs, the residual risk for kidney disease remains high in diabetic patients.12The annual loss of glomerular filtration rate (GFR) in patients with T2DM has been estimated at 5.2 ± 4.1 ml/min/1.73m2.13 An intense search for drugs that can decrease this residual risk and prevent development of diabetes- and/or non-diabetes-related CKD is ongoing. Nephroprotection is among the many metabolic and cardiovascular benefits of the new drugs for diabetes, SGLT2i and GLP-1 RA. These mechanisms are not entirely understood and depend on various mechanisms.
In pivotal studies, dulaglutide has been shown to prevent diabetic kidney disease (DKD) in pivotal clinical trials and in real-life situations. 7–9 In the current study at one year of treatment, patients who received dulaglutide had a lower decrease in eGFR than those who received insulin glargine (specifically −0.4 versus −0.9 mL/min/1.73 m2; p=0.0024). These values were based on an eGFR of 84.4±23.4 mL/min/1.73m2. Patients had a mean age of 59.5±10.9, HbA1c 8.2±1.7%, and were taking drugs that influenced the RAAS pathway by about 45%. Our work is novel in that it extends over 36M of treatment and confirms these previous findings. We started from a baseline eGFR of 88.1±26.47 mL/min/1.73m2 as calculated with the MDRD-4 formula, a mean age of 57.8±9.96, and an HbA1c 8.53±1.91%. Most of them (80%) received treatment with drugs that influenced the RAAS pathway.
It can be seen that in metabolic T2DM, baseline HbA1c levels decreased during the first year by 1.4%, levels that were maintained throughout the follow-up period and were comparable to the reduction observed in other studies. Regarding the maintenance of renal function, it can be observed that the eGFR was maintained in the overall number of patients in addition to the analysis of subgroups with concomitant treatments. We used the age-related decrease in GFR as a reference, which allowed us to observe that in the patients in our study, the loss of GFR was less than expected compared to the age-related value without considering the associated pathologies. In our study, the overall number of patients had a mean eGFR decrease of −4.85/mL/min/1.73m2 at 36M, which in a population with T2DM, could be compared to −15.6 mL/min /1.73m2 for the same time.13 In the subgroup analysis, we found that in the group in which patients received insulin, this drop in eGFR was more significantly pronounced at 36M than in the group without insulin (−5.39 versus −3.36 ml/min/1.73m2; p=0.006) as shown in Table 2. In the insulin subgroup, they started from a mean HbA1c value of 1% higher (8.87%±1.97% versus 7.81%±1.42%) and an eGFR that was clearly lower than the non-insulin group (82.81±28.33 versus 92±25.19 mL/min/1.73m2). The average age did not vary between both groups. HbA1c and the lower eGFR of the insulin group confirmed poorer metabolic control and the association with a greater decrease in eGFR.13 No differences were found in eGFR control in patients receiving metformin, DPP4i, or SGLT2i, from which it can be deduced that dulaglutide is effective in maintaining eGFR independently of other antidiabetic drugs. Furthermore, almost 80% of the patients took RAAS drugs as we have previously noted.
Conclusions Based on the 36M follow-up results, dulaglutide was shown to be an effective and nephroprotective drug in diabetic patients, allowing an metabolic control. These results are the first published real-life data obtained over an extended study period and allow us to confirm the beneficial results of dulaglutide in renal and metabolic functions.