GLP-1/GIP analogs: potential impact in the landscape of obesity pharmacotherapy

Figures & data

Figure 1. An overview of the biological actions of endogenous glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) in man. Tissue-specific effects of GLP-1 and GIP are provided for relevant organs in green or blue, respectively.

Table 1. A summary of GLP-1 R mimetics and GLP-1/GIPR co-agonists studied in obesity management.

Therapeutic Name	Administration Route	Mechanism of Action	Regulatory Approval/Development Stage	Study Duration (months)	Cohort Size	Endpoints Assessed	Weight Loss Outcome (%bw loss)	Reference
Liraglutide (Saxenda)	Injectable	GLP-1 R agonist	2019	24	846	BMI, WC, HbA1c, FPG, FPH, FPL, QOL	5–10	[37]
Semaglutide (Wegovy)	Injectable	GLP-1 R agonist	2021	5.5	1961	BW, BC, QOL	14.9	[18]
Semaglutide (Rybelsus)	Oral	GLP-1 R agonist	Phase III (commencing 2023)	5.5	198*	BMI, WC, VFM, HbA1c, FPL	-	[44]
Tirzepatide	Injectable	GLP-1 R/GIPR co-agonist	Phase III (T2DM)	12	1879	BMI, WC, QOL, FPL, FPG, HbA1c, HOMA-IR	7.6–11.2	[73]
RG7697	Injectable	GLP-1/GIPR co-agonist	Phase II	3	108	BW, HbA1c, FPG, FPL, FPH	2.86	[81]

Assessed endpoints include body mass index (BMI), waist circumference (WC) measurement, glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), fasting plasma hormones (FPH) encapsulating insulin, glucagon, and c-peptide measurements, quality of life (QOL) questionnaires, body composition (BC) as measured by dual-energy X-ray absorptiometry, visceral fat measurement (VFM) as measured by CT-scan and homeostatic model assessment for insulin resistance (HOMA-IR).

Figure 2. A peptidic structure analysis of glucose-dependent insulinotropic peptide (GIP) (1–42), glucagon-like peptide-1 (GLP-1) (7–36) and tirzepatide, a dual GIP/GLP-1 receptor co-agonist. Amino acid residues are provided as their single-letter abbreviations. Residues shared with GIP(1–42) are shaded in blue, shared with GLP-1(7–36) are shaded in green, residues shared with both GLP-1 and GIP are indicated in Orange and those unique to tirzepatide are shaded in gray. The fatty acid modification of tirzepatide is indicated in yellow. Receptor affinities are also indicated based on values reported in the literature [101] .

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