iiinova — where your digital self keeps evolving

David W (aka Flex NP) @rnflex.bsky.social · 22h

Beautiful article. Could see the yellowed edges on my run today as well. The sun is still warm but the cool breeze is a foreshadow for what's to come

010

David W (aka Flex NP) @rnflex.bsky.social · 23h

At least I have more time for other endeavors on Saturdays now! Cuz. Woof. That was ugly bad

001

David W (aka Flex NP) @rnflex.bsky.social · 02/10/2026

I know. How quickly that flipped. Also SGLT1i. Good idea. Bad side effects, but also partially successful Now we just shrug at Tirz and Reta getting 40-50% of patients back to normoglycemia

010

David W (aka Flex NP) @rnflex.bsky.social · 02/10/2026

Well it finally happened. Insurance required a prior authorization for Telmisartan. A medication that cash pay is anywhere from $13 to $40 a month. The system is just so broken

161

David W (aka Flex NP) @rnflex.bsky.social · 02/10/2026

Researching and writing about EASD and found these 2015 slides. I'm laughing because outside of glucokinase drugs(approved overseas, not US) none of these drug classes have gone anywhere. And I'M LAUGHING because now we advise GLP1 and SGLT2i drugs FOR ASCVD risk reduction. How fast things change.

220

David W (aka Flex NP) @rnflex.bsky.social · 02/10/2026

Same. That we've shifted so rapidly in how we treat diabetes is astonishing. Researching my next blog post and stumbled upon these slides from 2015. A year later we got the first CVOT data on semaglutide and EVERYTHING changed.

010

David W (aka Flex NP) @rnflex.bsky.social · 02/10/2026

Another day. Another diabetic who's down to Mounjaro and Crestor as their only meds. A1c 5.5% LDL is 77. Blood pressure is normal. UACR is 0. Lost 10% of body weight, now overweight BMI. Miracle drugs.

3171

Reposted by David W (aka Flex NP)

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

It has been a remarkable 24 hours in the world of diabetes and obesity medicine. First we saw the full readout of retatrutide for obesity. Then this morning retatrutide for type 2 diabetes. Both with historic weight loss. Now we can add Eloralintide+Tirzepatide combo to that list.

1135

David W (aka Flex NP) @rnflex.bsky.social · 01/10/2026

Absolutely we have. I agree. But I can't change society writ large. I can help individuals who want to weigh less. And arguably lack of access to the meds is also part of the problem you outlined.

100

David W (aka Flex NP) @rnflex.bsky.social · 01/10/2026

My diabetics who are down to Mounjaro and a statin and maybe one blood pressure med. My CKD and HF patients who have stabilized. Women able to get pregnant because the drugs seem to improve ovulation. Yes we have a problem with fat shaming but that's not the only "why" people want these drugs.

110

David W (aka Flex NP) @rnflex.bsky.social · 01/10/2026

Honest question, are you actually prescribing these drugs? Patients genuinely love the drug and results because they can live again. They can exercise. They can move with less pain. They can control their cravings. They take less drugs. Because you're describing a really negative scenario here.

310

David W (aka Flex NP) @rnflex.bsky.social · 01/10/2026

Well and GIP lowers leptin. Amylin turns up the central leptin signaling in the brain. Boom even better glycemic and decreased hepatic glucose production

010

David W (aka Flex NP) @rnflex.bsky.social · 01/10/2026

Honestly GIP + selective Amylin(AMY1r like Elora) may be enough.

110

David W (aka Flex NP) @rnflex.bsky.social · 01/10/2026

That's an ongoing battle. Access and cost remains the biggest issue. Most people DO not want to stop even if they reach a plateau. It's unique in that aspect. People love the drug for lack of better terms? But yes weight cycling is bad! Tell that to insurance companies who keep gatekeeping access.

100

David W (aka Flex NP) @rnflex.bsky.social · 01/10/2026

Yeah it's not every situation. But it has happened to a subgroup of my patients.

000

David W (aka Flex NP) @rnflex.bsky.social · 01/10/2026

Not sure tossing the eugenics bomb is appropriate here. We understand better than ever that excess adiposity is an independent risk factor for ASCVD, cancer and many other issues. I do talk movement and eating habits with my patients daily and shared decision rules my interactions.

000

David W (aka Flex NP) @rnflex.bsky.social · 01/10/2026

Perhaps context matters in the fact that we're biologically driven to eat and we've created an environment where we can get 500 calories snacks on every corner while also creating an environment where physical activity isn't needed. In that context it's self inflicted by humanity writ large

110

David W (aka Flex NP) @rnflex.bsky.social · 01/10/2026

Eloralintide trials are called Enlighten and diabetes trials of retatrutide are Transcend continuing the theme lol

030

David W (aka Flex NP) @rnflex.bsky.social · 01/10/2026

Their spouse being on a GLP-1. I've seen it multiple times now. One partner starts GLP1..The other Partner reflexively eats less and then boom they're losing weight!

410

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

And as I shared with you earlier but now I will publicly GLP1 + flozin even in established DKD can really delay progression!!

020

Reposted by David W (aka Flex NP)

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

These 24 hours will go down in medical history. A 4 act play. What's more incredible is ONE company did all of this in the last 5 years! 3 purposely designed drugs and suddenly we've solved essentially our oldest self inflicted ailment.

2112

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

Probably a few other metrics as well. My health system tracks ARB/ACE use in diabetics as well. My hyper responder GLP1 patients are only on tirzepatide+statin nowadays but I get naughty grams for "not controlling BP" when they're normoglycemic and normotensive 😂🙄

130

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

Add liver cirrhosis and by extension liver transplant to this in the next few years as well with the rise of multi agonist GLP1/GIP and/or glucagon drugs. Obesity related cancers as well over the longer term(20 years)

053

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

2112

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

Yes to the point that I've got into arguments with older providers that I'm being too aggressive with my A1c goals because so many of my patients are 6% or lower. Nah. Just letting the drugs cook. Tirzepatide + SGLT2i + low dose metformin. And now this on the horizon.

140

Reposted by David W (aka Flex NP)

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

In 24 hours we've seen one company, Eli Lilly, show us they've essentially solved obesity from a pharmacology standpoint. Take your pick it'll work. From a diabetic and obesity standpoint, bariatric surgery isn't the only option anymore. We can do it with pharmacology.

162

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

At this point the biggest hurdle is access and cost. We've finally figured out how to make folks metabolically healthy again but the cost, literally, is too high. Hopefully that barrier can be breached soon as well.

040

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

Their next combo with Eloralintide is a drug called Macupatide. It's a GIP monoagonist. In phase 1 trials this drug had zero side effects. It increases insulin sensitivity, lower glucose and body weight. And now it gets combined with Eloralintide. It'll cause 20% weight loss with no side effects.

221

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

And to be clear I'm paraphrasing the Eli Lilly leadership team. A few months back they said they'd solved obesity. I thought it was hubris and corporate speak. It was not. No one else is even close at this point and they're not slowing down.

110

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

162

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

Additionally they showed a few details from a phase 1 trial in obese patients with Eloralintide and Tirzepatide and it basically provided better weight loss than even retatrutide. Low dose EloraTirz 3mg/5mg causes 17% weight loss in 16 weeks 😳😳 insanity.

110

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

Blood pressure showed modest reductions. Side effects were dose dependent. Higher doses had more side effects. Discontinue rates were 10-27% but Lilly didn't give details. We're probably in the retatrutide weeds again. Bunch of people have excessive body weight loss.

110

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

A1c reductions were even more wild. There was an additive effect of Elora + tirzepatide with a reduction up to 2.9%!! Rate of diabetic remission was upwards of 70% in some arms 😳😳😳 @mikejohansenmd.medsky.social

151

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

The weight loss results were as good OR BETTER THAN RETATRUTIDE in only 48 weeks with many of the combo arms still losing weight at the 48 week mark. Weight loss was roughly additive My mind is blown.

130

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

This was a phase 2 trial in diabetics. Average A1c was 8.1, it was about 50/50 male/female split, and average BMI was 38. Dosing was mixed. Some Eloralintide alone, then various combos of the two drugs combined.

120

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

1135

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

It's both. Pain reduction happens before weight loss(inflammation reduction) then continues to improve with weight loss

010

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

In the way we dose it now yes. Making it uni molecular with a GLP1 agonist would completely change how the body takes it up and where it interacts.

120

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

This WHOLE video will help you understand a lot of this, retatrutide etc. But if you're interested in the estrogen stuff it gets a quick mention around the 47 minute mark as to why.

youtu.be

"Evolution of Natural Hormones to Transform Drug Treatment of Obesity" Richard DiMarchi, PhD

YouTube video by A. Alfred Taubman Medical Research Institute

120

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

Oh my God. Eli Lilly just presented Eloralintide+Tirzepatide for Type 2 diabetes and it's even better than retatrutide for A1c and weight loss. Slides soon. This was my actual reaction in my office:

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

It's estrogen. Helps kick up the weight loss. There's a science group that's been trying to figure out how to combine GLP1 + estrodiol into one shot so that the estrodiol only goes where the GLP1 goes. Preclinically it causes massive weight loss.

252

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

Crazy effective drug. bsky.app/profile/rnfl...

010

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

What more can I say? They created a Godzilla monster of a drug. RIP my mentions again. Hopefully it should be approved for diabetes and weight loss by this time next year. @proptermalone.bsky.social

050

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

Side effects were again in line with every other incretin out there. Dysesthesia rate was 7% nausea signal was fairly muted and diarrhea was actually the leading SE. Minimal hypoglycemia and no ketoacidosis signal.

120

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

An LOL reduction in inflammation, 40% drop in triglycerides again, ~10% drop in LDL cholesterol even tho average LDL was 90md/dl is still a big deal. UACR dropped and GFR again rose as measured by Cystatin-C. It's fixing everything.

110

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

Worried about blood sugar because it contains glucagon? Worry not and laugh again @mikejohansenmd.medsky.social ending fasting glucose was ~100. Fasting insulin dropped 45% !!!! As noted 40% of 9mg/12mg ended up in diabetic remission HOMA IR dropped >50% again.

112

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

Just bonkers weight loss again. 1/3 of patients on the higher doses lost >25% over 50% of patients went from obese to just overweight. (BMI<30) The waterfall plots go so hard here again.

120

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

And they just posted the diabetes data this morning which I'm working on posting. RIP my mentions yet again today

210

David W (aka Flex NP) @rnflex.bsky.social · 30/09/2026

Yeah. I am team Telmisartan for anyone with MetS, prediabetics or diabetes or dyslipidemia. Which is most patients. Only reach for losartan for really uncontrolled gout cuz the half life sucks. Valsartan reluctantly in HFrRF for the ARNI combo.

000