How long have GLP-1 (Glucagon-like peptide-1) receptor agonist weight loss drugs, such as semaglutide (semaglutide) and liraglutide (liraglutide), been available for the treatment of type 2 diabetes in adults with a history of obesity?

History of GLP-1 Receptor Agonists for Weight Loss

Liraglutide 3.0 mg (Saxenda) became the first GLP-1 receptor agonist approved by the FDA for chronic weight management in December 2014, followed by semaglutide 2.4 mg (Wegovy) in June 2021, and tirzepatide (Zepbound) in November 2023. 1, 2

Timeline of FDA Approvals

For Type 2 Diabetes Treatment:

• GLP-1 receptor agonists were originally developed and marketed for glycemic control in type 2 diabetes before their weight loss applications were formally recognized 2
• Liraglutide at lower doses (up to 1.8 mg daily) was approved for type 2 diabetes management prior to its obesity indication 3
• Semaglutide 1.0 mg was approved for type 2 diabetes before the higher 2.4 mg dose received obesity approval 1

For Obesity Management:

• December 2014: Liraglutide 3.0 mg daily (Saxenda) became the first GLP-1 receptor agonist approved by the FDA specifically for chronic weight management in adults with BMI ≥30 kg/m² or ≥27 kg/m² with at least one weight-related comorbidity 1, 2
• June 2021: Semaglutide 2.4 mg weekly (Wegovy) received FDA approval for obesity treatment, demonstrating superior weight loss (14.9%) compared to liraglutide 1
• November 2023: Tirzepatide (Zepbound), a dual GIP/GLP-1 receptor agonist, was approved for obesity management, achieving the highest weight loss of 20.9% 1

Evolution of Clinical Use

Early Recognition (Pre-2014):

• Clinical trials evaluating GLP-1 receptor agonists for type 2 diabetes consistently demonstrated weight loss as a secondary benefit, prompting investigation of higher doses specifically for obesity treatment 2
• Research from 1970-2016 documented the weight loss effects of these medications in patients with and without diabetes 4

Current Landscape (2014-Present):

• Over the past decade since liraglutide's obesity approval, the class has expanded to include more potent agents with superior efficacy profiles 1, 5
• The progression from liraglutide (6.1% weight loss) to semaglutide (14.9% weight loss) to tirzepatide (20.9% weight loss) represents approximately 10 years of therapeutic advancement 1, 6

Key Clinical Context

Mechanism Understanding:

• These medications work through multiple pathways including hypothalamic appetite suppression, delayed gastric emptying, increased glucose-dependent insulin release, decreased glucagon secretion, and increased pancreatic β-cell growth 1
• The weight loss effects were recognized during diabetes trials but required dedicated obesity trials and higher dosing to achieve FDA approval for weight management 2

Comparative Efficacy Over Time:

• Liraglutide 3.0 mg (approved 2014): 5.24-6.1% weight loss 1, 6
• Semaglutide 2.4 mg (approved 2021): 14.9% weight loss 1, 6
• Tirzepatide 15 mg (approved 2023): 20.9% weight loss 1