Natural products, particularly those derived from plants are serving as promising lead compounds. Plant-based preparations are the critical contributor in today’s field of medicine, due to their ease of use, low cost, and lack of side effects.9 As per as the recent study by Salehi et al. several medicinal plants that have been traditionally utilized in the treatment and management of diabetes.10Table 1 outlines the results of recent studies on herbal complementary therapy, which demonstrate significant complementary effects after the co-administration or simultaneous administration of natural products such as isolated natural compounds and extracts from different parts of plants alongside commercially available drugs.

Recent studies have suggested that polysaccharides derived from natural sources may be beneficial in anti-diabetic therapy, due to their strong antioxidant properties.5,11,12 An investigation of anti-diabetic therapy in alloxan-induced diabetic rats found that a combination of polysaccharide isolated from the roots of Acanthopanax senticosus (200 mg/kg/BW) and metformin (2 mg/ kg/BW) was more effective than metformin alone in relieving diabetes symptoms and healing liver and kidney damage.13

One such example of plant namely Gymnema sylvestre was reported to have promising hypoglycemic and blood cholesterol-lowering properties.14 In a study, rats with induced diabetes were given a dose of 400 mg/kg of Gymnema Sylvestre leaf extract alongside 0.8 mg/kg of Glimepiride for a period of 28 days. The results showed a marked increase in anti-hyperglycemic and anti-hyperlipidemic activity. Further, concomitant administration of the leaf extract in conjunction with glimepiride produces a greater decrease in HbA1c levels in the blood and an increase in serum insulin levels compared to glimepiride taken alone.15

The use of Azadirachta indica (AZI) has been documented since ancient times for its ability to treat a range of illnesses. Recent evidence suggests that extracts from both the leaf and bark of this plant may reduce blood glucose levels and improve the lipid profile.16 However, when combining Glipizide (GZ) with AZI leaf extract, it is recommended to exercise caution. In a study involving streptozotocin-induced diabetic rats, administering either of two doses of AZI extract (250 mg/kg) or a combination of extract and GZ (5 mg/kg) decreased the bioavailability of GZ and its subsequent hypoglycemic effect.17

The use of garlic as a nutritional and medicinal supplement has been gaining recognition around the world.18 The study conducted by R. Kumar et al. revealed that a combination of garlic (250 mg) and metformin (500 mg) was more effective at decreasing the blood glucose level of obese diabetic patients than metformin alone. In addition, the participants in the study had a noticeable improvement in their lipid profiles. Additionally, Studies have found that combining garlic and metformin may help to reduce the nephrotoxicity associated with gentamycin.19,20

Further, Gliclazide is a common treatment for type 2 diabetes mellitus, yet it has been demonstrated that its efficacy declines with time. This is attributed to the progressive linear decline in β-cell function that occurs with the disease.21 Considering this issue several researches has been carried out to potentiate the efficiency of Gliclazide with combination of herbal drugs. In a study conducted by Vastavai et al., healthy rats and rabbits were co-administered gliclazide (100/200 mg/kg) and curcumin (2/4 mg/kg). Surprisingly, there was a marked decrease in the animals’ blood glucose levels after multiple doses, and the combination proved to be more effective than gliclazide alone in terms of overall therapeutic effects.22 Further a study states that when streptozotocin induced diabetic rats were administered gliclazide and quercetin together, their glucose homeostasis, lipid profile, and inflammatory status were improved. Additionally, insulin immunostaining in their beta cells returned to normal levels.24

Figure 1:
Flow Chart of the study selection process.

Studies have indicated that a combination of Annona squamosa leaf extract and various concentrations of Glipizide (300 mg/kg, 3.75 mg/kg, 2.5 mg/kg, 1.25 mg/kg) given to streptozocin-induced diabetic rats on a high-fat diet can lead to a reduction of their blood glucose levels by 25-50%. This could potentially decrease the need for Glipizide.24,25 Additionally, co-administering leaf extract of Brassica rapa (turnip) with metformin has been reported to improve hypoglycemic activity in diabetic rats.26,27