Pharmacologic Therapies for Obesity: The Future is Here

Aug 26, 2023

Pharmacologic Therapies for Obesity: The Future is Here

Join us in this expert podcast as we delve into the captivating world of GLP-1 receptor agonists (GLP-1RAs), exploring their profound impact on weight management and cardiometabolic effects. We also discuss the potential cardiovascular benefits affecting patients with obesity and cardiovascular disease.

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Content

4.68 -> Welcome back to the Mayo

6.82 -> Clinic Cardiovascular Podcast Series,

8.74 -> interviews with the experts.

10.54 -> I'm our host, Sharon Hayes.

12.26 -> I'm a non invasive cardiologist

14.06 -> and vice share faculty development and

15.86 -> academic advancement for

17.4 -> the Department of Cardiovascular Medicine

19.78 -> here in Rochester, Minnesota.

21.46 -> Today I'm joined by Dr. Kyla Lara.

24.38 -> She is a preventive cardiologist and

26.28 -> echocardiography important for today's topic.

29.34 -> Co director of the cardioboliclinicdpic

34.5 -> is pharmacologic therapies for obesity.

37.28 -> The future is here.

38.46 -> Welcome Kyla.

39.83 -> Thank you so much Dr. Hayes.

41.54 -> It's such a pleasure to be here

42.76 -> talking about something I'm very

44.08 -> passionate about and a lot

45.58 -> of people out there

46.28 -> want more information of yeah,

49.14 -> obesity is big, literally and figuratively,

52.76 -> it's so prevalent and it particularly

54.84 -> affects our patients,

56.38 -> our cardiovascular patients.

58.74 -> We have some new therapies that are exciting,

61.94 -> but I think because

62.74 -> they are new cardiologists

63.86 -> want to know a little bit more how they work,

65.8 -> who is the right patient

67.48 -> that should receive them.

68.98 -> So tell us about that.

71.16 -> Absolutely. Thank you for that question.

74.06 -> And we know that obesity

75.94 -> more and more research is coming

77.62 -> out that it's a very complex disease.

79.34 -> It's really more than calories

80.78 -> in and calories out.

82.14 -> I'm sure you've had patients

83.66 -> before that have tried everything

85.14 -> in terms of lifestyle interventions

86.86 -> and they really give

87.52 -> it their greatest effort.

88.58 -> But we know with every decade of life,

90.56 -> our resting energy expenditure and

92.86 -> our caloric requirements really decrease.

95.6 -> A lot of things make it very

97.54 -> challenging to lose weight.

99.02 -> And we're in an era now with

100.54 -> these new weight loss medications that were

103 -> originally developed for diabetes,

106.2 -> where it's really going to transform how

108.34 -> we treat obesity as a chronic disease.

110.32 -> And it's very exciting for

111.46 -> us cardiology providers because we know

113.66 -> that within

114.92 -> our cardiovascular disease patients

117.26 -> that many of them,

118.3 -> many of them suffer from obesity.

119.98 -> And a lot of the symptoms

121.495 -> are intertwined, right?

122.89 -> With cardio vascular symptoms,

124.41 -> shortness of breath, chest pain,

125.85 -> reduced exercise tolerance, and

127.51 -> deconditioning that comes from obesity.

129.77 -> And so it's really important that

131.29 -> we understand these medications and

132.93 -> also identify appropriate patients

135.03 -> so to prevent the misuse of

137.05 -> these medications and really target

139.57 -> the correct patient population that would

141.41 -> really benefit from these.

143.89 -> And so I'm really excited to talk with them,

146.19 -> talk with you about them, excuse me.

149.25 -> So the indication for

152.85 -> weight loss really came from treating

154.55 -> diabetics and realizing they were

156.55 -> losing weight and sometimes

157.73 -> too much weight, honestly.

159.07 -> And so how do they work?

160.59 -> And what are we seeing as

162.03 -> the short and long term benefits?

163.89 -> And the side effects are consequences.

166.15 -> Absolutely.

167.19 -> And so there are two main classes of these,

169.67 -> new GLP one receptor agonist and the dual

172.47 -> GLP one IP dual medication.

175.99 -> The GLP one receptor agonist,

177.99 -> there's a daily dose,

179.41 -> if you have diabetes it's called Victoza,

181.61 -> and if you don't have

182.87 -> diabetes it's called Saxenda.

184.87 -> What it is is the generic word

187.03 -> or the name is Lyriglutide.

189.63 -> That is our daily injectable.

191.63 -> And what they found in the studies

193.69 -> are that in diabetics and non diabetics,

195.83 -> there's about a 5% weight loss.

197.93 -> From there, they develop more drugs weekly

200.55 -> injectables under the name Semaglutide.

204.34 -> Semaglutide. When you reach

206.48 -> the target doses that were seen in

207.96 -> the trials of 2.4 mg,

209.9 -> you're seeing upwards of

211.08 -> about 15% weight loss

213.1 -> in patients without diabetes

214.6 -> and around 10% in patients with

216.58 -> concomitant diabetes at 68 weeks or so.

219.7 -> Then the newest kids on

221.08 -> the block is Trizepatide,

222.6 -> also known as Manjaro.

224.32 -> This is the dual medication.

226.48 -> It has a GLP, one receptor agonism,

228.6 -> and it also has GIP.

230.2 -> The synergistic mechanism of

233.66 -> them working together in

235.26 -> the trials actually showed weight loss of

237.4 -> about 20 to 25% at 72 weeks,

240.36 -> which is pretty comparable

241.58 -> to bariatric surgery.

243.185 -> Now to go back to talk

245.47 -> about what do these medications even do?

248.45 -> So they're both cretins which

250.71 -> are naturally produce hormones by your gut.

253.45 -> Glp one or glucagon like peptide one and

257.43 -> GIP or

258.63 -> glucose dependent insulinotropic peptide.

261.93 -> They are released by

263.55 -> your gut after you have a meal.

265.85 -> And then this hormone will then go to

268.21 -> multiple places as a pathway.

271.35 -> Activators, the most important ones are

273.89 -> obviously the original

275.77 -> indication was for diabetes.

277.67 -> It goes to the pancreas.

278.89 -> It improves insulin sensitivity and

281.17 -> decreases glucogon secretion

282.97 -> from the eyelid cells.

284.25 -> It also goes to your brain.

286.21 -> The theory right now is it goes to

287.93 -> the hypothalamus to decrease

289.63 -> appetite and also importantly,

291.69 -> it decreases thirst.

292.85 -> So very important to

294.91 -> talk to our patients when

296.03 -> we're putting them on these drugs.

297.43 -> If they're on concomitant diuretics

299.63 -> and have underlying C KD,

301.83 -> that it does decrease thirst.

303.81 -> Lastly, it goes to your gut

305.77 -> and it decreases the motility.

307.59 -> So all of the side effects are

310.05 -> basically from this decrease

311.81 -> in motility in the gut.

313.59 -> You can imagine if you have

315.29 -> a couple eggs or an omelet for breakfast.

317.85 -> Or hopefully steel cut oats for breakfast.

320.63 -> Instead of that food passing and

322.87 -> digesting within 30 min to an hour.

325.49 -> That food will sit

326.47 -> there over the course of the day.

327.77 -> So by the time snack time,

329.29 -> lunchtime, afternoon, snack, dinnertime.

332.01 -> And maybe if you're a midnight eater,

333.93 -> the portions in which

334.97 -> you would otherwise consume

336.25 -> normally are going to be

337.53 -> cut by a significant amount.

339.41 -> And so hence you're taking

340.63 -> in less calories as well.

342.21 -> And so that's how they work

345.15 -> to improve diabetes control

347.47 -> and also for weight loss.

349.27 -> Just talk briefly about

351.07 -> side effects because I think we hear about

352.99 -> that and that's why the doses

355.01 -> are increased gradually.

356.79 -> I understand.

357.84 -> Absolutely. Yes. And similar to

360.45 -> the trials is how our

361.75 -> standard clinical practices,

363.29 -> we start at the very lowest dose and we

365.69 -> increase every four weeks

368.23 -> after four doses, once weekly injections.

370.73 -> And the most common side effects from

373.01 -> the decrease in gut motility

374.71 -> are going to be nausea,

376.27 -> vomiting, constipation, diarrhea, pretty bad,

380.23 -> upset stomach and abdominal cramping.

382.51 -> If you have a history of

383.73 -> gallstones or pancreatitis,

385.49 -> you're at more risk for

386.73 -> having these complications.

388.31 -> A lot of patients who also

389.79 -> have concomitant IBS,

391.45 -> or irritable bowel syndrome,

392.91 -> or any kind of irritable bowel

394.35 -> disease will have to

395.49 -> be very careful about how

397.01 -> we titrate these medications.

398.965 -> And all of these side effects

401.74 -> can be pretty uncomfortable,

405.62 -> to say the least, but they're

407.2 -> mild to moderate in terms of severity.

409.78 -> The more severe reactions are going to

411.8 -> be pancreatitis or gallstone pancreatitis.

416.1 -> And then if you have a family history or

417.86 -> a personal history of any thyroid cancers,

420.42 -> if you have a family history of men

422.54 -> to syndrome or EN two syndrome,

425.26 -> then there was a very small tick in

428.74 -> the studies that showed there is

430.42 -> an association with increased risk for those.

433.26 -> A lot of those need to

434.66 -> be discussed with the patients.

436.15 -> And then again, I can't emphasize enough in

438.4 -> our cardiovascular patients with obesity,

440.52 -> a lot of them have underlying CK D,

442.66 -> so it's really important to get

443.88 -> a baseline creatinine on them.

445.52 -> Know their renal function,

446.74 -> knowing that one of the side effects

448.28 -> is to decrease the thirst.

449.62 -> And if you have a patient

450.86 -> on Lasix or ferrosirsomideumt,

453.92 -> you're giving these medications.

455.68 -> Understand that their diuretics

457.62 -> may need to change as they lose weight.

459.78 -> We might need to change these diuretics

461.96 -> and monitor that creatine as well.

464 -> And that goes the same for,

465.32 -> we know with significant weight loss

467.32 -> or clinically meaningful weight loss,

468.98 -> which is defined as

470.44 -> at least 5% weight loss or more

473.05 -> your requirements

474.38 -> for blood pressure medications,

475.88 -> beta blockers, et cetera,

477.4 -> all of those can change.

478.48 -> So it's really important

479.8 -> in our very special population of

481.84 -> at least cardio vascular patients

483.76 -> to really work with

485.14 -> a provider who understands

487.38 -> that with this weight loss.

488.94 -> And it can be significant,

490.18 -> which is the goal that careful down,

492.7 -> titration and monitoring of

494.18 -> these drugs is happening.

495.66 -> At the same time, we've

498.54 -> talked about some of the secondary endpoints,

501.88 -> I guess, related to cardiovascular benefit.

504.76 -> With the weight loss, we may

506.24 -> have a drop in blood pressure,

507.5 -> less more easy to control,

509.28 -> or even back off on the meds.

511.28 -> What are the other data about

513.5 -> cardiovascular benefits in terms

516.22 -> of actually had points?

518.96 -> Are there any yet, right?

521.04 -> And that is the most

523.24 -> important question that all of us in

525.14 -> cardiovascular medicine are

526.78 -> itching to know currently.

529.78 -> Based on the scientific evidence,

531.72 -> all of the evidence is in

533.08 -> secondary prevention and

534.28 -> high risk type two diabetics.

536.08 -> And what they found from these large trials

538.34 -> is hard end points

540.02 -> and decrease of Mace events,

541.52 -> or the major adverse cardiovascular events,

545 -> atheromatous plaque

547.64 -> improvement in renal function,

549.4 -> and improvement in all of

550.44 -> those cardio metabolic factors.

552.76 -> In addition to the pathways I mentioned,

556.56 -> these medications are associated,

560.16 -> at least in the animal models

561.68 -> right now, of anti inflammatory,

563.4 -> improving endothelial function and really

566.18 -> having all these cleotrophic effects

567.98 -> that we're still learning more.

569.46 -> It's very exciting. I heard from

571.38 -> a little birdie that

572.62 -> I believe at AHA this year

574.7 -> they're going to come out with

575.96 -> a select trial which is

577.84 -> basically looking at Semaglutide

579.96 -> and hard Mace outcomes.

581.96 -> So we'll have an idea of how these drugs

585.18 -> affect our cardiovascular patients

587.38 -> without diabetes,

588.72 -> which is going to really change the way

591.28 -> that we treat obesity

592.86 -> and cardio vascular disease.

594.36 -> And it's really exciting.

595.68 -> One thing that I've noticed since we

597.36 -> launched our cardio metabolic clinic,

599.555 -> whenever you start these medications,

601.85 -> one of the side effects is there's

603.97 -> a trend and increased heart rate.

606.03 -> Now, there hasn't been

607.35 -> any association with increased arrhythmia,

609.49 -> but patients will send me

610.77 -> patient portal messages saying, hey,

612.55 -> I just want you to know,

613.57 -> My resting heart rate

614.73 -> is around 85 or 90.

616.47 -> I'm losing weight, I'm feeling good.

618.59 -> But I did notice my heart rate is increasing.

620.91 -> What that means, we have

622.21 -> no idea at this point, but good to know,

624.81 -> we have a lot of data for the benefits,

627.41 -> even in adolescence, for bariatric surgery.

630.63 -> Will these drugs, do you

632.83 -> predict, because you're an expert?

634.45 -> Will they replace bariatric surgery?

636.79 -> Be alongside them?

638.73 -> Where are the roles for

640.45 -> both of these treatments?

642.03 -> Yeah, that's a question.

644.19 -> Many people have surgeons,

646.53 -> non surgeons alike.

647.71 -> And the answer is,

648.89 -> I think both have a role.

651.19 -> Definitely. We know that in a lot of

653.63 -> the select trials for Semaglutide,

656.05 -> they did extensions as to what happens when

658.49 -> you discontinue these

659.63 -> medications at one year.

661.19 -> And it's what you think happens,

663.43 -> patients will gain weight there.

666.23 -> They looked at it

667.71 -> extra year after and what they

669.07 -> found was patients still had a net negative,

671.51 -> about 5% weight loss.

673.33 -> But they do lose all of

675.13 -> those cardio metabolic benefits

676.99 -> once they regain that weight,

678.29 -> once they stop these medications.

680.25 -> Unlike bariatric surgery for the most part,

682.69 -> this is an irreversible depending

684.73 -> on the type of

685.25 -> weight loss surgery you undergo.

687.01 -> Type of transformative type of surgery

691.09 -> to change that gut

692.61 -> brain metabolism and how you mal,

695.07 -> absorbed a lot of nutrients and

697.13 -> obviously calories to lose the weight.

699.83 -> And I think that it's important

703.65 -> to have a medication like

705.41 -> the GLP one receptor agonist as a first step,

708.01 -> especially in

708.65 -> our cardiovascular patients who have

710.69 -> a high operative risk for bariatric surgery.

714.11 -> I think for the younger patients

715.91 -> with longer lifespan,

717.13 -> thinking about the long term effects

719.23 -> of these drugs over decades,

720.53 -> we don't have any date on that.

723.13 -> But we do know from bariatric surgery,

725.19 -> all of those heart end points

726.75 -> all cause mortality,

727.91 -> et cetera, or improve with bariatric surgery.

730.77 -> But for

731.09 -> our adult congenital heart disease patients,

732.97 -> for our patients who

733.67 -> have had reduced sternotomyes,

735.15 -> who are obese and they can't work

737.07 -> out because of their cardiovascular symptoms.

739.25 -> And I think medications would probably be

741.21 -> the best, least risky.

743.83 -> At least for those patients.

745.37 -> But definitely a role for both.

747.17 -> Yeah.

747.75 -> And I think also consideration of cost.

749.49 -> Obviously surgery has a big upfront cost

751.73 -> and there's some ongoing follow up,

753.15 -> but we're committing patients to

755.19 -> daily or weekly injections that currently

757.99 -> are very expensive for a long time.

760.71 -> Because just like when

762.47 -> patients stop taking their statins,

764.41 -> their cholesterol goes back to baseline,

766.91 -> my understanding is you stop taking

768.89 -> these and your weight will drip up as well.

771.59 -> Absolutely. And so right now,

774.53 -> because of the demand

775.99 -> for the drug and the shortage,

779.27 -> it's heartening and disheartening

781.93 -> because for the patients

782.93 -> who need it the most,

783.79 -> a lot of our patients who are

785.03 -> 65 and older who are

786.83 -> under state insurance or

788.29 -> governmental aid right now,

790.21 -> obesity related treatments by

792.51 -> medications are unfortunately not approved.

795.07 -> And so this is

796.59 -> something that I think will hopefully

798.77 -> change in the future to provide

801.16 -> this opportunity for

802.34 -> our most vulnerable patients.

804.3 -> And I think something to put out there is,

807.62 -> you know, these medications,

808.94 -> you see them in the news.

810.02 -> Ozempic, Wegovy, you know, Mounjaro,

813.16 -> a lot of shaming and I have

815.4 -> Ozempic face and this celebrity is taking it.

818.72 -> And so it's really important to not make

821.12 -> any judgments about whether or

822.52 -> not an obese patient,

824.12 -> a relative yourself is taking it.

826.34 -> We understand that all of the data shows that

829.72 -> behavioral modification

832.06 -> lifestyle intervention over

833.84 -> the long term is not sustainable in

835.68 -> the current infrastructure of

837 -> a convenient society is ours,

839.14 -> where we're telling people to go out there.

843.72 -> Single parents, parents who

845.48 -> work night time shifts,

847 -> parents who have no time,

848.36 -> they're single parents having

850.08 -> to cook and clean and do everything,

852.12 -> and then telling them to go work out

853.6 -> for 45 min and

855.3 -> to go grocery shopping

857.14 -> every week for perishables that are healthy.

859.54 -> You know, when you have calorie dense,

862.34 -> ultra processed foods at

864 -> wits End right next to them,

866.36 -> cheap as can be, and you're telling them

868.2 -> to lose weight and have the willpower.

870.02 -> I think we have to get with the program and

872.92 -> understand that right now the

874.84 -> way our society is, it's very,

877.1 -> very difficult if you don't

878.38 -> have the socioeconomic means

880.88 -> to live that type of lifestyle that

883.28 -> we need to embrace these medications.

885.74 -> Just like you said, we don't do any shaming

888.46 -> on patients who take statins

889.96 -> who still enjoy their red meat.

891.48 -> We don't tell patients

893.8 -> who enjoy eating out with high sodium foods.

897.22 -> Why are you taking

898.16 -> blood pressure medications?

899.48 -> And that's the same way we

900.66 -> need to treat obesity.

901.88 -> It's more than just calories

903.36 -> in and calories out.

904.44 -> And I really hope to

906.36 -> contribute to everybody out there

909.54 -> and destigmatizing that obesity is

911.9 -> just shutting your mouth and exercising more.

915.26 -> My last question, I just want

917 -> to say what kinds of

918.16 -> patients a really perfect

921.84 -> for your cardio metabolic clinic,

924.4 -> who are the ones who are going

925.62 -> to be benefited the most?

927.2 -> And we cardiacologistho

930.58 -> should we be sending to you?

932.22 -> Absolutely.

933.44 -> Currently, we are trying to help

936.66 -> the most vulnerable patients who we

939.86 -> know obesity has a high association

941.88 -> with their cardiovascular disease.

943.84 -> Those diseases are going

946.56 -> to be atrial fibrillation.

947.84 -> We know there's a strong association

949.84 -> with obese patients

951.16 -> who have atrial fibrillation.

952.78 -> We know that heart failure with

954.18 -> preserved ejection fraction has

956.48 -> a very high and strong association

958.74 -> with obesity.

960.775 -> Patients who have heart failure

963.25 -> with reduced ejection fraction,

964.77 -> these patients are trying to get to

966.25 -> LVAD or they're trying to get to transplant.

968.53 -> And we know there are BMI cutoffs

970.27 -> depending on what part of

971.31 -> the country you're at to

972.29 -> be a candidate for that.

974.25 -> And if you're too big then hey,

976.07 -> you're not going to get listed.

977.25 -> So those are patients that we would

979.03 -> like to see too obviously.

981.07 -> They're going to be more sensitive.

982.51 -> They're going to be more

984.13 -> challenging patients that we have to

985.83 -> really hold their hand and make sure that

987.91 -> we're watching the titration

989.27 -> and the side effects,

990.29 -> like I said, with

991.09 -> those diuretics and other medications.

993.26 -> And then lastly, adult

995.59 -> congenital heart disease

996.93 -> patients here at Mayo,

998.65 -> we have a very special group that takes care

1001.55 -> of these patients who've had

1002.81 -> four fifth sternotomyes.

1004.39 -> They're in their '20s '30s and

1005.81 -> their BMI's are above 40.

1007.81 -> And they have high operative mortality with

1010.25 -> really high gradients across their conduits,

1013.55 -> across prosthetic valves, You name it.

1015.83 -> There's the phenomena

1017.43 -> of patient prosthesis mismatch,

1019.35 -> where patients are symptomatic, obese,

1021.59 -> and they have high gradients

1022.85 -> across their prosthesis,

1023.99 -> but maybe with weight loss,

1025.45 -> those gradients can decrease

1027.61 -> along with their symptoms.

1028.75 -> And these are the patients we're

1030.55 -> obviously focusing on right now.

1032.85 -> We understand that coronary disease pots,

1036.19 -> I mean any disease that's

1037.87 -> associated with obesity

1039.25 -> probably will benefit.

1040.53 -> But in terms of having that,

1042.41 -> needing a special expert

1044.13 -> from a cardiology led program,

1046.73 -> it's going to be those higher risk patients

1049.17 -> and obviously coronary disease as well.

1051.13 -> Because we know even with stable angina and

1053.07 -> stable coronary disease patients can be

1055.29 -> obese and deconditioned and they're

1057.41 -> constantly having repeat stress echoes.

1059.93 -> They're having other kind of

1061.35 -> non invasive functional testing to

1063.51 -> really rule out what is causing

1065.47 -> their symptoms when maybe it's the obesity.

1068.29 -> I'm just excited about these drugs.

1070.13 -> I'm excited about your clinic and I'm

1071.85 -> really grateful for you

1073.65 -> sharing your expertise today.

1075.61 -> So thank you for joining us.

1077.57 -> Thank you so much, Dr. Hayes.

1079.07 -> It was such a pleasure and thank

1080.21 -> you everyone for listening.

1081.63 -> This wraps up this week's episode

1083.85 -> of interview with the experts.

1085.09 -> And I'd like to thank Dr. Lara again for

1087.33 -> joining me today and

1088.41 -> discussing this important topic.

1090.03 -> We look forward to you joining us again

1092.55 -> next week for another interview

1094.53 -> with an expert. Well

Source: https://www.youtube.com/watch?v=GI2oL4Qoi10