GLP-1 analogs lower blood sugar by two main mechanisms:

1) Stimulating Insulin Secretion:
GLP-1 analogs bind to and activate GLP-1 receptors present on the beta cells of pancreas. This stimulates the secretion of insulin from these cells in a glucose-dependent manner. In response to high blood glucose levels after a meal, these medications induce release of appropriate amounts of insulin to maintain euglycemia.

2) Reducing Glucagon Secretion:
GLP-1 also suppresses the secretion of glucagon hormone from alpha cells of pancreas. Glucagon causes increase in blood sugar levels by stimulating hepatic glycogenolysis and gluconeogenesis. Reduction in glucagon levels by GLP-1 analogs helps in glycemic control.

3) Delaying Gastric Emptying:
Binding of GLP-1 analogs to receptors in the central and peripheral nervous system results in delayed gastric emptying and reduced appetite. Slower gastric emptying prevents sudden surge in blood glucose levels after eating while reduction in appetite helps in weight control over long term.

Efficacy and Safety
Clinical trials have established the superior glycemic control provided by Glucagon Like Peptide 1 Analogs analogs either as monotherapy or when used along with other anti-diabetic drugs. They are highly effective in lowering HbA1c levels, especially in combination with basal insulin. Some key trials are discussed below:

AWARD-1 Trial:
The trial compared Liraglutide 1.2mg and 1.8 mg doses to placebo and glimepiride in over 3000 patients. HbA1c reduction was seen to be 1.12% and 1.45% for 1.2mg and 1.8mg doses respectively compared to 0.81% in placebo group. Liraglutide also showed significant weight loss.

LEAD-6 Trial:
Trial compared Dulaglutide's efficacy to insulin glargine in over 1600 patients inadequately controlled with metformin. Dulaglutide 0.75mg and 1.5mg reduced HbA1c by 1.16% and 1.45% respectively compared to 0.94% for Glargine with concurrent weight loss rather than gain.

HARMONY Outcomes Trial:
The trial assessed cardiovascular safety of Albiglutide used along with standard care in over 9400 patients with type 2 diabetes and cardiovascular risk factors. Results showed Albiglutide to be non-inferior to placebo for reducing major cardiovascular events.

Overall, GLP-1 analogs are well tolerated with transient gastrointestinal side effects being most common. Their better efficacy, weight reducing ability and neutral or positive effect on cardiovascular system make them an attractive therapy for optimal diabetes care and management.

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