|
| 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 |
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