Efficacy and safety of dulaglutide versus first-line hypoglycemic agents in Asian patients with type 2 diabetes: a systematic review and meta-analysis

Research results and study characteristics

The original 457 articles were searched, and duplicate literature was first removed with EndNote software, then the literature was further read for screening, and finally, the 5 studies that met the inclusion criteria were included.21,22,23,24,25. Of these, four were RCTs and one was a retrospective observational study. A total of 2344 Asian patients with T2DM, mainly from Asian countries and regions including China, Japan, India, Korea and Taiwan, were involved. Dulaglutide has two doses (0.75 mg and 1.5 mg/subcutaneous injection and once weekly), first-line hypoglycemic drugs included liraglutide (0.9 or 1.2 mg/day, orally ), glimepiride (1 or 3 mg/day, orally), and Insulin Glargine (subcutaneous injection, once daily). Meanwhile, the duration of intervention in 3 studies21,22,26 was 26 weeks. One study had two follow-up cycles (26 weeks and 52 weeks) and another the duration was 13 weeks. All studies were published from 2015 to 2020. The literature selection process and results are shown in Fig. 1. Table 1 describes the basic characteristics of the selected studies.

Figure 1

Flowchart of the studies searched for in this meta-analysis.

Table 1 General characteristics of included studies.

Quality assessment

The results of the quality assessment of 5 studies are shown in Fig. 2. Four studies were RCTs21,22,23,24 with good quality; one study was a retrospective observational study but of lower quality than the others. Additionally, 3 RCTs 21,22,24 describes detailed randomization methods, allocation concealment, blinding of participants and personnel, incomplete outcome data, and other biases. An RCT 23 contained details of blinding of participants and staff, and other biases. Relevant information from a study 25 was ambiguous. The moderate risks of study design bias are shown in Fig. 3.

Figure 2
Figure 2

Assessment of the quality of the risk of bias of the studies.

picture 3
picture 3

Risk of bias graphs for studies.

Efficiency analysis

HbA1c

Changes in HbA1c from baseline between dulaglutide (0.75 mg and 1.5 mg) and first-line hypoglycemic drugs are shown in Fig. 4. Both dose groups of dulaglutide markedly reduced HbA1c levels. [Dulaglutide 0.75 mg: WMD = − 0.20, 95% CI (− 0.28, − 0.11), P < 0.0001; Dulaglutide 1.5 mg: WMD = − 0.49, 95% CI (− 0.67, − 0.30), P < 0.0001] of patients from Asia. We removed one study 25 to ensure a high level of heterogeneity in the dulaglutide 1.5 mg group, heterogeneity then decreased significantly without affecting the overall results [WMD = − 0.56, 95% CI (− 0.66, − 0.46), P < 0.0001].

Figure 4
number 4

Forest plot comparing HbA1c between dulaglutide and first-line hypoglycemic agents.

FBG

There were no statistically significant differences in FBG [Dulaglutide 0.75 mg: WMD = 0.17, 95% CI (− 0.34, 0.69), P = 0.51; Dulaglutide 1.5 mg: WMD = 0.31, 95% CI (− 0.85, 0.24), P = 0.27] between dulaglutide (0.75 mg and 1.5 mg) and first-line hypoglycaemics.

Weight

Two doses [Dulaglutide 0.75 mg: WMD = − 1.43, 95% CI (− 2.38, − 0.48), P = 0.003; Dulaglutide 1.5 mg: WMD = − 2.12, 95% CI (− 2.71, − 1.53), P < 0.0001] significantly reduced the body weight of Asian patients, compared to those in control groups. Initially, the heterogeneities of two doses of dulaglutide were observed high, but when we withdrew one study21 in the dulaglutide 0.75 mg group and a study25 in the dulaglutide 1.5 mg group, the heterogeneities in the two groups were remarkably reduced. Moreover, the results of the global estimation [Dulaglutide 0.75 mg: WMD = − 1.87, 95% CI (− 2.15, − 1.60), P < 0.0001; Dulaglutide 1.5 mg: WMD = − 2.40, 95% CI (− 2.68, − 2.13), P < 0.0001] were not affected.

Arterial pressure

No statistically significant difference was noted in systolic blood pressure and diastolic blood pressure for Asian patients with T2D between dulaglutide (0.75 mg and 1.5 mg) and first-line hypoglycemic drugs. The results are shown in Table 2.

Table 2 Efficacy and safety results in the meta-analysis.

Security analysis

Adverse events

The incidence of adverse events [RR = 1.09, 95% CI (1.01, − 1.18), P = 0.02] in the dulaglutide 0.75 mg group was slightly higher than that of first-line hypoglycaemics. However, there was no statistically significant difference in the incidence of adverse events [RR = 1.12, 95% CI (0.94, − 1.35), P = 0.21] in the dulaglutide 1.5 mg group compared to first-line hypoglycaemics. The change in the incidence of adverse events from baseline between dulaglutide (0.75 mg and 1.5 mg) and first-line hypoglycemic drugs is shown in Fig. 5.

Figure 5
number 5

Forest plot comparing adverse events between dulaglutide and first-line hypoglycaemic drugs.

Serious Adverse Events

The difference was statistically not significant in the incidence of serious adverse events [RR = 1.35, 95% CI (0.77, 2.36), P = 0.29] between dulaglutide 0.75 mg and control groups. The incidence of adverse events [RR = 2.03, 95% CI (1.17, 3.53), P = 0.01] in the dulaglutide 1.5 mg group was slightly higher than that of first-line hypoglycaemics.

Hypoglycemic episodes

The incidence of hypoglycaemic episodes in both dulaglutide (0.75 mg and 1.5 mg) groups was higher than that of first-line hypoglycaemic drugs. The results are shown in Table 2.

Other Adverse Events

After consuming dulaglutide, most patients experienced loss of appetite, diarrhea, nausea, and abdominal distension. Compared to first-line hypoglycemic agents, the dulaglutide 1.5 mg group showed a greater incidence of loss of appetite, diarrhea, nausea and abdominal distention, and the dulaglutide 0.75 mg group did not show significant difference on these three aspects. Meanwhile, there were no statistically significant differences in the incidence of kidney and urinary disorders, psychiatric disorders, eye disorders, heart disorders, endocrine disorders, nervous system disorders, and neoplasms between the dulaglutide (0.75 mg and 1.5 mg) and first-line hypoglycaemic drugs. . On the other hand, the dulaglutide 0.75 mg group showed a higher incidence of reproductive system disorders, but no difference between the dulaglutide 1.5 mg group and the control group was observed (Table 2).

Publication bias

Stata 12.0 software was used for publication bias analysis of HbA1c, FBG, body weight and adverse events in patients after drug consumption. Beggs’ tests did not find significant publication bias in the studies (P= 0.806, P = 0.462, P = 0.807, P = 0.991, respectively). The results are shown in Fig. 6.

Figure 6
number 6

Publication bias of primary outcome indications.

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