Table 3.

Commonly prescribed drugs to manage DM [98].

Drug class	Examples	Mechanism of action	Side effects	Relationship with retinopathy
Biguanides (metformin) [98, 99]		Oral lowers glucose production in the liver, improves the body's sensitivity to insulin	Nausea, abdominal pain, bloating, diarrhoea	Retrospective reviews suggest that metformin may have protective effects against DR
Incretins [98, 100] (glucagon-like peptide 1 agonists)	Dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide	Predominantly injection, sometimes oral mimic the action of glucagon-like peptide 1: (i) stimulate pancreatic islet β-cell insulin production (ii) impair glucagon secretion (iii) slow gastric emptying	Nausea, vomiting, diarrhoea, possible hypoglycaemia, but usually only when taken concurrently with other medications	May result in transient worsening of DR Case reports: (i) dramatic deterioration of DR from background retinopathy to bilateral PDR and DME (ii) rates of complications significantly higher with semaglutide
Gliptins (DPP4 inhibitors) [98, 101]	Alogliptin, linagliptin, saxagliptin, sitagliptin, vildagliptin	Oral inhibition of DPP4 (responsible for the breakdown of incretins), which enhances their action	Hypoglycaemia when taken concurrently with other medications or in combination form; upper respiratory tract infection, gastrointestinal upset, headache, skin irritation	Case reports suggest that they may reduce rates of DR progression, use of <1 year may be associated with early worsening of DR, sitagliptin showed delay and prevention of DR
Sodium glucose cotransporter-2 (SGLT2) inhibitors [98, 101]	Canagliflozin, dapagliflozin, empagliflozin, ipragliflozin	Oral tablets: reduce renal tubular glucose reabsorption, producing a reduction in blood glucose without stimulating insulin release [102]	Urinary tract infection, genital infection, hypoglycaemia	Slows progression of retinopathy in rat models, marked regression of DME after 16 weeks in case reports on ipragliflozin
Thiazolidinediones [98]	Pioglitazone, rosiglitazone	Oral: activates the gene that regulates lipid and glucose metabolism	Weight gain, fluid retention (ankle oedema), cardiac failure, bone fractures	Rosiglitazone use associated with a 59% relative risk reduction in progression to PDR over 3 years and lower rates of VA loss, may reduce inflammatory markers, and increased markers of angiogenic activity also reported the increased risk of DMO
Sulfonylureas [98, 99]	Gliclazide, glimepiride, glibenclamide, glipizide, glyburide, tolbutamide	Oral: insulin secretagogue that binds to sulfonylurea receptors in beta cells	Hypoglycaemia, weight gain	Gliclazide more so than others may prevent DR deterioration and progression to PDR and seems to have additional effects

Adapted from Saw 2019, diabetes UK, and Mayo Clinic unless otherwise cited.