Table 4.

Future agents in clinical trials.

Trial name or authors	Number of patients	Enrollment criteria	Duration of trial	Results	Other information
Survodutide
Blüher M, Rosenstock J et al.32,a	Total = 413 (411 treated) Survodutide DG1 = 50, DG2 = 50, DG3 = 52, DG4 = 50, DG5 = 51, DG6 = 50 Semaglutide = 50 Placebo = 59	-ages 18–75 years -type 2 diabetes (HgB A1c 7.0–10.0%); on metformin -BMI 25–50 kg/m2	16 weeks	A1c reduction DG1 = −0.91%. DG2 = −1.46%. DG3 = −1.71% DG4 = −1.56% DG5 = −1.63% DG6 = −1.86% Body weight reduction-up to −8.7% (DG6)	AE 77.7% of survodutide treated participants (mainly gastrointestinal)
SYNCHRONIZE-1 (NCT06066515)	Estimated 600	-at least 18 years old -BMI of 30 kg/m2 or more or BMI of 27 kg/m2 with one health problem related to weight -at least one self-reported unsuccessful dietary effort to lose weight	76 weeks	PENDING	RECRUITING 1:1:1 Survodutide 3.6 mg v 6.0 mg v. placebo Primary endpoint: -% change in body weight from baseline to Week 76 -achievement of body weight reduction ≥ 5% from baseline to Week 76
SYNCHRONIZE-2 (NCT06066528)	Estimated 600	-at least 18 years old -BMI of 27 kg/m2 w or more -diagnosed with T2DM with HgBA1c 6.5%–10.0% -currently treated for T2DM with either diet and exercise alone or stable treatment (for at least 3 months prior to screening) -at least one self-reported unsuccessful dietary effort to lose weight	76 weeks	PENDING	RECRUITING 1:1:1 Survodutide 3.6 mg v. 6.0 mg v. placebo Primary endpoint: -% change in body weight from baseline to Week 76 -achievement of body weight reduction ≥ 5% from baseline to Week 76
Pemvidutide (ALT-801)
MOMENTUM	Total = 391 Pemvidutide 1.2 mg = 40 Pemvidutide 1.8 mg = 40 Pemvidutide 2.4 mg = 41 Placebo = 39	-ages 18–75 years -BMI of 30 kg/m2 or more or BMI of 27 kg/m2 with one obesity-related comorbidity -non-diabetes, HgB A1c ≤ 6.5% and fasting glucose ≤ 125 mg/dL -at least one unsuccessful weight loss attempts -minimal of approximately 35% of subjects were to be male	48 weeks	Body weight reduction Pemvidutide 1.2 mg = −10.3% Pemvidutide 1.8 mg = −11.2% Pemvidutide 2.4 mg = −15.6% Placebo = −2.2%	-Gastrointestinal AE similar to phase I trials and other NuSH therapies -Glucose homeostasis maintained
IMPACT (NCT05989711)	Estimated 190	-ages 18–75 years old -histologic diagnosis of NASH and/or histologic confirmation of NASH based on central pathology evaluation of a liver biopsy during screening -BMI ≥ 27 kg/m2 -met 3 of the 5 criteria of metabolic syndrome -liver fat content by MRI-PDFF ≥ 8%	24 weeks		RECRUITING 1:1:1 Pemvidutide 1.2 mg v. Pemvidutide 1.8 mg v. placebo Primary endpoint: -proportion of subjects achieving NASN resolution with at least 2-point reduction in NAS without worsening of fibrosis -proportion of subjects achieving at least 1 stage of improvement in liver fibrosis without worsening of NASH
Efinopegdutide
Alba, M, Yee, J et al.85	Total = 343 Efinopegdutide 5.0 mg = 43 Efinopegdutide 7.4 mg = 81 Efinopegdutide 10.0 mg = 72 Liraglutide 3.0 mg = 95 Placebo = 52	-ages 18–70 years -BMI 35–50 kg/m2	26 weeks	Body weight reduction Efinopegdutide 5.0 mg = −8.5% Efinopegdutide 7.4 mg = −9.8% Efinopegdutide 10.0 mg = −11.8% Liraglutide 3.0 mg = −7.0% Placebo = −1.8%	The most common AE with treatment of efinopegdutide were gastrointestinal related (mainly nausea)
Di Prospero, N, Yee, J et al.86	Total = 195 (144 completed) Efinopegdutide 5.0 mg = 33 Efinopegdutide 7.4 mg = 30 Efinopegdutide 10.0 mg = 32 Placebo = 47	-ages 18–70 years -BMI 35–50 kg/m2 -T2DM (A1c 6.5–9.5% treated with diet and exercise alone or up to 2 oral antihyperglycemic agents)	12 weeks	Body weight reduction Efinopegdutide 5.0 mg = −5.3% Efinopegdutide 7.4 mg = −6.5% Efinopegdutide 10.0 mg = −7.9%	The most commone AE with treatment of efinopegdutide were gastrointestinal related (mainly nausea)
AMG 133 (MariTide)
NCT05669599	Total = 592	-age ≥ 18 years old -BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 and previous diagnosis of one of the following co-morbidities: HTN, dyslipidemia, OSA, CVD -Cohort B, HgBA1c ≥ 7% and ≤ 10% with established diagnosis of T2DM for 180 days prior to screening either treated with diet and exercise or on stable treatment with metformin, sulfonylurea, or sodium-glucose cotransporter 2 -history of at least one unsuccessful dietary effort to lose weight	52 weeks		ACTIVE NOT RECRUITING Cohort A (without diagnosis of type 1 or T2DM): receive AMG 133 or placebo in 1 of 7 dose cohorts Cohort B (with diagnosis of T2DM): receive AMG 133 or placebo in 1 of 7 dose cohorts Primary endpoint -percent change from baseline to week 52 in body weigh
Danuglipron
Saxena AR, Frias JP et al.30	Total = 411 (316 completed treatment) Danuglipron 2.5 mg BID = 68 Danuglipron 10 mg BID = 68 Danuglipron 40 mg BID = 71 Danuglipron 80 mg BID = 67 Danuglipron 120 mg BID = 71 Placebo = 66	-ages 18–75 years old -T2DM diagnosis treated with diet and exercise with or without metformin use -HgB A1c between 7.0% and 10.5% -BMI 22.5 (Asia) or 24.5 kg/m2 (North American and Europe) to 45.4 kg/m2	16 weeks	HgB A1c reduction: −0.49% to −1.18% v. −0.02% for placebo Body weight reduction: 80 mg BID: mean −2.04 kg 120 mg BID: mean −4.17 kg Body weight not statistically significant in lower doses	Safety -most common TEAE were nausea, diarrhea, and vomiting -TEAE associated with higher disease of danuglipron
NCT04707313	Total = 630 Cohort 1 (1 week titration to target dose) Danuglipron 40 mg BID Danuglipron 80 mg BID Danuglipron 120 mg BID Danuglipron 160 mg BID Danuglipron 200 mg BID Placebo Cohort 2 (2 week titration to target dose) Danuglipron 120 mg BID Danuglipron 160 mg BID Danuglipron 200 mg BID Placebo Cohort 3 (4 week titration to target dose) Danuglipron 80 mg BID Danuglipron 140 mg BID Danuglipron 200 mg BID	-ages 18–75 years old -BMI ≥ 30 kg/m2 -stable body weight, defined as < 5 kg change for 90 days before visit 1	Cohorts 1&2: approximately 9 months Cohorts 3: Approximately 10 months	Body weight reduction: −6.9% to −11.7% v. +1.4% for placebo (at 32 weeks) −4.8 to −9.4% v. + 0.17% (at 26 weeks)87	Most common AE were mild (up to 73% nausea, up to 47% vomiting, up to 25% diarrhea)87 -High discontinuation rates >50% in all disease v. placebo with 40%87
Efpeglenatide
AMPLITUDE-M88	Total = 406 Efpeglenatide 2 mg = 100 Efpeglenatide 4 mg = 101 Efpeglenatide 6 mg = 103 Placebo = 102	Inadequately controlled T2DM (A1c ≥ 7 and ≤10%)	56 weeks	Baseline to week 30, A1c reduction 2 mg: −0.5% 4 mg: −0.8% 6 mg: −1.0% A1c reduction seen at week 30 was maintained at week 56 Body weight reduction, more significant in both 4 mg and 6 mg dose, −2.3 kg and −2.2 kg respectively	GI events most commonly reported AE. Incidence increased with dose.

AE, adverse events; T2DM, type 2 diabetes mellitus; NASH, non-alcoholic steatohepatitis; MRI-PDFF, magnetic resonance imaging-proton density fat fraction; HTN, hypertension; OSA, obstructive sleep apnea; CVD, cardiovascular disease; BID, twice daily; TEAE, treatment-emergent adverse eve.

^aDG (dose group) 1–4, up to 0.3, 0.9, 1.8 or 2.7 mg once weekly; DG 5 and 6, 1.2 or 1.8 mg twice weekly.