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The top 5 papers from NEJM, Lancet & Nature—decoded in plain English.
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In adults with type 1 diabetes and obesity, tirzepatide caused an average 10.3 kg (22.7 lb) weight loss over 12 weeks compared to just 0.7 kg in the placebo group - that's nearly 9% of their body weight lost.
Snaith JR, Frampton R, Samocha-Bonet D, Greenfield JR
GLP-1 receptor agonists prevent heart attacks entirely through metabolic improvements like better blood sugar (37% contribution) and weight loss (29% contribution), with no direct protective effect on the heart itself.
Tong J, Li N, Hu F, Yue Y
In older adults with type 2 diabetes, GLP-1 receptor agonists and SGLT-2 inhibitors slowed frailty progression by 0.007 and 0.005 points respectively on a 0-1 frailty scale compared to DPP-4 inhibitors over one year.
Park CM, Thanapluetiwong S, Chen X, Oh G, Ko D, Kim DH
Among diabetic patients on hemodialysis, GLP-1 drugs reduced dementia risk by 18% compared to DPP-4 inhibitors, with 10.2% developing dementia versus 11.2% after 2 years.
Le D, Kilpatrick M, Kraft WK, Grams ME, Jaar BG, Shin JI
After California expanded Medicaid to older undocumented immigrants in 2022, their access to newer diabetes drugs like GLP-1s increased 6% faster per month than documented patients, eventually reaching similar prescription levels by study's end.
Ro AE, Morales C, Jiang L, Choi JM, Tavares Kuhn N, Wu C
Brain stimulation therapy (rTMS) produced weight loss of 8.2 kg after one year, matching semaglutide's 5.7 kg loss and dramatically outperforming SGLT2 inhibitors' modest 2.0 kg loss in people with diabetes and obesity.
Ferrulli A, Senesi P, Sonaglioni A, Cannavaro D, Massarini S, Macrì C, Cipponeri E, DeFronzo RA, Luzi L
In 724 people with type 2 diabetes, beta-cell function (but not alpha-cell function) predicted blood sugar control, with every standard deviation improvement in C-peptide index reducing the risk of poor glycemic control by 17%.
Kahn SE, Tripputi M, Lachin JM, Balasubramanyam A, Banerji MA, Barzilay J, Cohen RM, Garvey WT, Gramzinski MR, Rasouli N, Rhee M, Seegmiller JC, Singh V, Sivitz WI, Steffes MW, Utzschneider K, DeFronzo RA, GRADE Research Group*
Semaglutide reduced hospital stays by 11% in people with obesity and heart disease, preventing 2 hospitalizations and 19 hospital days per 100 patients per year.
Nicholls SJ, Ryan DH, Deanfield J, Ferreira D, Lang CC, Lincoff AM, Lingvay I, Lübker C, Terns PP, Rasmussen S, Stensen S, Weeke PE, Kahn SE, SELECT Trial Investigators
Semaglutide helped adults with Type 1 diabetes and obesity reduce their daily insulin dose by 22.6% over 26 weeks, with early effects being mostly due to the drug itself rather than weight loss.
Karakus KE, Akturk HK, Kruger D, Ahmann A, Bharvaga A, Langel CR, Ackeifi CA, Rosen J, Pyle L, Snell-Bergeon JK, Shah VN
In older adults with type 2 diabetes, GLP-1 medications reduced dementia risk by 24% compared to DPP4 inhibitors but increased risk by 53% compared to SGLT2 inhibitors over 2-3 years of follow-up.
Zhou T, Tang H, Zhang B, Zhang D, Lu Y, Li L, Chen J, Chen Y, Asch DA, Chen Y
GLP-1 medications reduce major limb complications by 30-34% in people with peripheral artery disease and diabetes, while cutting amputation risk in half across broader diabetes populations.
Dutta D, Mahajan K, Kamrul-Hasan ABM, Mahajan N, Sharma M, Vohra S
Ultra-processed breakfast foods triggered 67% higher insulin levels and increased hunger sensations compared to regular processed foods, regardless of whether people were normal weight or overweight.
Çelik MN, Ulug E
GLP-1 receptor agonists, traditionally used for diabetes and obesity, show promise as treatments for neurodegenerative diseases like Alzheimer's and Parkinson's by breaking the harmful cycle of brain inflammation and metabolic dysfunction.
Spezani R, Mandarim-de-Lacerda CA
Tirzepatide helped 57% of people with type 2 diabetes hit 3 or more key health targets compared to just 34% with semaglutide - like having a more precise tool that hits multiple bullseyes at once.
Neves JS, Leite AR, Vale C, Marques P, Vasques-Nóvoa F, Leite-Moreira A, Ferreira JP
Combining two nutrients (lauric acid and L-tryptophan) delivered directly into the small intestine reduced peak blood sugar by 1.3 mmol/L in men with type 2 diabetes by slowing stomach emptying and boosting gut hormones.
Anjom-Shoae J, Fitzgerald PCE, Rose BD, Bitarafan V, Rehfeld JF, Horowitz M, Feinle-Bisset C
Tirzepatide performed just as well as dulaglutide in preventing heart attacks, strokes, and cardiovascular deaths in 13,165 diabetes patients, with 12.2% versus 13.1% experiencing these major events.
Nicholls SJ, Pavo I, Bhatt DL, Buse JB, Del Prato S, Kahn SE, Lincoff AM, McGuire DK, Miller D, Nauck MA, Nishiyama H, Nissen SE, Sattar N, Weerakkody G, Wiese RJ, Zinman B, Zoungas S, Basile J, Davies MJ, Giorgino F, Kellerer M, Ji L, Varkonyi T, Menon V, Broder JC, Herschtal A, D'Alessio D, SURPASS-CVOT Investigators
Among UK patients first identified with obesity, 58% already had at least one obesity-related complication, yet only 6% received weight-loss medications or surgery - revealing a massive treatment gap.
Khunti K, Capehorn M, Artime E, von Arx LB, Davies AL, Adam A, Lampropoulou A
Mazdutide, a dual-hormone diabetes drug, beat dulaglutide by lowering blood sugar an extra 0.24-0.30% and causing 3.78-5.76% more weight loss over 28 weeks in Chinese adults with type 2 diabetes.
Guo L, Zhang B, Xue X, Zhang X, Cai H, Jiang H, Zhang L, Jin P, Wang X, Cheng Z, Zhang S, Geng J, Guo Y, Hu H, Ma Q, Li L, Du H, Han-Zhang H, Xue F, Deng H, Qian L, Yang W, DREAMS-2 investigators
Mazdutide, a dual-action diabetes drug, reduced blood sugar by 2.15% (HbA1c) and caused 7.81% weight loss in 24 weeks - both results that probably weren't just luck (p<0.0001).
Zhu D, Zhao J, Cai H, Chu X, Xiu S, Song C, Cheng Z, Cao H, Jiang H, Zhang L, Wang H, Shi B, Li Y, Liu M, Feng B, Xue F, Deng H, Li H, Li L, Li Y, Ma Q, Qian L, DREAMS-1 Investigators
GLP-1 medications increase injection-site reaction risk by 3.5 times compared to other treatments, with exenatide and dulaglutide showing the highest rates of injection-site bleeding.
Taj S, Zuber M, Rashid M, Chhabra M, Undela K, Rawal S, Villa Zapata L
Switching from multiple daily insulin injections to once-daily iGlarLixi helped type 2 diabetes patients lose 4.2 kg while maintaining the same blood sugar control and cutting their insulin dose by nearly 29 units per day.
Novodvorský P, Thieme L, Laňková I, Franková Š, Veselá A, Záhumenský E, Edelsberger T, Löblová M, Žižka O, Vytasil M, Lauand F, Bonnemaire M, Hrubý F, Mráz M, Haluzík M
Researchers discovered that reducing bile acids in mice prevented diet-induced obesity while selectively blocking absorption of saturated fats but preserving healthy polyunsaturated fats.
Chan AP, Jarrett KE, Lai RW, Brearley-Sholto MC, Cheng AS, Taveras MO, Iwata AM, Steel ME, Lau A, Whang EC, Kennelly JP, Gao Y, Rubert GE, Schmidt HM, Smith EP, Su B, Williams KJ, Tarling EJ, de Aguiar Vallim TQ
Patients using semaglutide through telehealth lost an average of 16.6% of their body weight over 68 weeks, with women achieving significantly better results than men.
Tchang B, Broffman L, Manalac R, Chai S, Samonas N, Barnes M, Allison DB
China has approved five new GLP-1 receptor agonists since 2021 for weight management, dramatically expanding obesity treatment options, but faces challenges with diagnostic criteria, policy targets, and over-reliance on medications.
Pan XF, Fang ZZ, Zhang L, Pan A
The ZEUS trial enrolled 6,376 high-risk patients with heart disease, kidney disease, and inflammation to test whether blocking interleukin-6 with ziltivekimab can prevent heart attacks, strokes, and kidney decline - results still pending.
Ridker PM, Baeres FMM, Hveplund A, Engelmann MMD, Hovingh GK, Lincoff AM, Marx N, Navar AM, Sattar N, Tuttle K, Perkovic V
Four clinically available medications (resmetirom, semaglutide, tirzepatide, and dapagliflozin) successfully reversed fatty liver disease with inflammation in 3,173 patients, with liver inflammation scores improving by 1.27 points on average compared to placebo.
Wood E, Akande R, Iqbal I, Albert SG
A major economic analysis found that popular weight-loss drugs like semaglutide (Ozempic/Wegovy) and liraglutide (Saxenda) are not cost-effective for treating obesity in people without diabetes, with negative returns of $3,659 to $84,060 per patient depending on the comparison.
Dhippayom T, Meraz M, Lee H, Hur C, Inadomi JM, Veettil SK, Dunn JD, Chaiyakunapruk N
A massive analysis of nearly 94,245 people found that GLP-1 medications like Ozempic and Mounjaro don't meaningfully increase or decrease cancer risk, with thyroid cancer odds only 37% higher (but this could easily be due to chance).
Ko A, Chang YC, Bahar F, Wang TH, Xanthavanij N, Yu CC, Hsieh RJ, See XY, Lo SW, Song J, Hsia YP, Chiang CH, Xu X, Lin S, Chiang CH
Adults with obesity lost an average of 8.2 kg (7.3% of their body weight) in just 12 weeks on low-dose tirzepatide, with nearly half achieving clinically meaningful 5%+ weight loss.
Angelopoulos N, Androulakis I, Rizoulis A, Boniakos A, Fousteris E, Mentzelopoulou V, Petkova V, Paparodis R, Zianni D, Florakis D, Korakovouni A, Mouslech Z, Livadas S, Tzoulis P
Among nearly 14 million Medicare patients with type 2 diabetes, Black patients were 28% less likely and patients in the most socially vulnerable neighborhoods were 7% less likely to start the breakthrough diabetes drugs semaglutide or tirzepatide compared to their more advantaged counterparts.
Decker SRR, Chaudhary RS, Inoue K, Song Y, Ndumele CE, Khan SS, Kazi DS
Among 160 women with diabetes who accidentally used GLP-1 medications around conception, there were no increased risks of birth defects, stillbirth, preterm birth, or small babies compared to insulin users.
Chou YC, Weng SH, Cheng FS, Tseng CH, Hu HY, Liu CH
Oral semaglutide slowed kidney function decline by about 0.4 mL/min/1.73m² per year compared to placebo in people with type 2 diabetes, but didn't significantly reduce major kidney complications over 4 years.
Mann JFE, Marx N, Deanfield JE, Emerson SS, Inzucchi SE, McGuire DK, Mulvagh SL, Pop-Busui R, Poulter NR, Engelmann MDM, Hovingh GK, Belmar N, Idorn T, Jeppesen OK, Birkenfeld AL, Amod A, Mankovsky B, Desouza C, Gorgojo-Martinez JJ, Arechavaleta R, Tu ST, Buse JB, SOUL Study Group*
Bangladeshi patients with type 2 diabetes lost 6.3% of their body weight and dropped their HbA1c from 7.6% to 6.5% while taking tirzepatide during Ramadan fasting, with no cases of dangerous low blood sugar.
Rahman MH, Selim S, Afsana F, Hoque MA, Saifuddin M, Alam MS, Sharifuzzaman M, Hannan MA, Hasan MN, Kamrul-Hasan ABM, Mustari M, Ahammed A
This is an erratum correcting author affiliation information - no research findings are reported in this correction notice.
Eldor R, Avraham N, Rosenberg O, Shpigelman M, Golan-Cohen A, Cukierman-Yaffe T, Merzon E, Buch A
Scientists developed a drug combination that activates gut hormone-producing cells so effectively that it created higher levels of satiety hormones than bariatric surgery achieves in Phase 1 human trials.
Sebhat IK, Murphy MJM, Zheng S, Lovelett RJ, Engelstoft M, Kosinski D, Yang X, Dunn V, Whang J, Lombardo MG, Heilbut A, Terracina G, Nicholas N, Leitner M, Consolati MJ, Chan B, Poterewicz G, Vance A, Liu J, Weber AE, Lauring B, Thornberry N, Pinto S
Bariatric surgery beats GLP-1 drugs for weight loss by an extra 10.3% of total body weight at 2 years, though the gap narrows to just 9.1% - except tirzepatide performs so well it's statistically tied with surgery.
Sabatella L, Ortega PM, Azcárate VV, Sastre FR, Pagola AU, Ahmed A, Purkayastha S, Ojanguren CT, Asensio NB, Landecho MF
The WHO has issued its first-ever global guidelines recommending GLP-1 therapies combined with intensive behavioral therapy for treating obesity, recognizing it as a chronic disease affecting over 1 billion people worldwide.
Celletti F, Farrar J, De Regil L
Liraglutide helped people with fatty liver disease lose weight (BMI improvement with 85% standardized effect) and improve liver function markers like GGT, but came with mostly manageable stomach side effects.
Kong W, Fang B, Xing W
Adding automated insulin delivery to GLP-1 medications lowered HbA1c by an extra 0.5% compared to standard care, while preventing the typical 1.9 kg weight gain seen with insulin intensification.
Graham TE, Raghinaru D, Afreen S, Ahmann A, Haidar A, Raskin P, Tsoukas MA, Lum JW, Sasson-Katchalski R, Pinsker JE, Beck RW, 2IQP Study Group*
Popular diabetes medications GLP-1 agonists and DPP-4 inhibitors carry a small 15-22% increased risk of gallbladder problems but don't increase pancreatitis risk compared to SGLT-2 inhibitors.
Fang YE, Paik JM, Ortega-Montiel J, Tesfaye H, Wexler DJ, Patorno E
People with fatty liver disease who achieved liver healing on tirzepatide lost twice as much weight (16% vs 7%) and had dramatically better blood sugar control than those who didn't respond.
Caussy C, Cusi K, Rosenstock J, Bugianesi E, Thomas MK, Tang Y, Mather KJ, Loomba R, Sanyal AJ, Hartman ML
Nearly 1 in 4 people (23.8%) with hard-to-control type 2 diabetes have excess cortisol production, which may explain why their blood sugar stays high despite multiple medications.
Buse JB, Kahn SE, Aroda VR, Auchus RJ, Bailey T, Bancos I, Busch RS, Christofides EA, DeFronzo RA, Eilerman B, Findling JW, Fonseca V, Hamidi O, Handelsman Y, Miller HJ, Ownby JG, Parker JC, Philis-Tsimikas A, Pratley R, Rosenstock J, Shanik MH, Sloan LL, Umpierrez G, Tudor IC, Schlafly TK, Einhorn D, CATALYST Investigators*
A new peptide called NN501 produces weight loss similar to GLP-1 drugs but works primarily by ramping up fat burning rather than reducing appetite, and mice kept the weight off better when treatment stopped.
Feetham CH, Groom S, John LM, Christoffersen BO, Collabolletta V, Lyons D, Adamson A, Lundh S, Gerstenberg MK, Tang-Christensen M, Conde-Frieboes KW, Secher A, Kruse Hansen AM, Luckman SM
Liraglutide, a diabetes drug, showed no effect on brain metabolism in Alzheimer's patients but improved executive function scores by a small but statistically significant amount over 52 weeks.
Edison P, Femminella GD, Ritchie C, Nowell J, Holmes C, Walker Z, Ridha B, Raza S, Livingston NR, Frangou E, Love S, Williams G, Lawrence R, Mcfarlane B, Archer H, Coulthard E, Underwood BR, Koranteng P, Karim S, Bannister C, Perneczky R, Prasanna A, Junaid K, McGuinness B, Nilforooshan R, Macharouthu A, Donaldson A, Thacker S, Russell G, Malik N, Mate V, Knight L, Kshemendran S, Holscher C, Mansouri A, Chester-Jones M, Holmes J, Tan T, Williams S, Ashraf A, Brooks DJ, Harrison J, Hinz R, Tadros G, Passmore AP, Ballard C
After following 32,542 people with type 2 diabetes for over 6 years, researchers found no difference in dementia risk between those taking GLP-1 drugs versus SGLT2 inhibitors - both groups had about 3.5% develop dementia.
Anagnostakis F, Kokkorakis M, Nagarajan S, Anastasiou G, Mantzoros CS
Saudi adults with type 2 diabetes taking oral semaglutide for 34-44 weeks saw their HbA1c drop by 1.0 percentage point and lost an average of 4.4 kg (9.7 pounds), with nearly 62% reaching their blood sugar target.
ElBadawi H, Albalkhi N, Al Kadhim I, Elsadig A, Baltzis D, Hatahet MH, Ismail M, Khader S, Rasmussen CL, Scheuer SH, Shalaby A, Almehthel M
SGLT-2 inhibitors and GLP-1 receptor agonists most consistently transform dangerous heart fat (epicardial adipose tissue) from inflammatory troublemaker to metabolic helper, reducing thickness and promoting healthy fat browning.
Heuboeck E, Bhogal CS, Mandl M
Semaglutide helped obese teens lose 16.7 percentage points more BMI than placebo while dramatically improving insulin sensitivity by 35% and multiple heart health markers over 68 weeks.
Arslanian S, Gies I, Goldman B, Karlsson T, Kelly AS, Skalshøi Kjær M, Körner A, Noureddin M, Wabitsch M, Harder-Lauridsen NM, Weghuber D
Tirzepatide helped 86-100% of Japanese patients with obesity lose at least 5% of their body weight after 72 weeks, with women and those with lower starting BMI showing the biggest weight losses (up to 24.9% body weight reduction).
Yokote K, Fukushima Y, Shingaki T, Oura T, Ogawa W
Massive analysis of 101,732 people taking GLP-1 drugs like Ozempic and Victoza found no increased thyroid cancer risk, with only 1 case per 10,000 patient-years reported in real-world surveillance.
Vilsbøll T, Stellfeld M, Aroda VR, Dandanell S, David JP, Kristiansen CTP, Rasmussen S, Roberts FL, Hegedüs L