Complete Guide to Peptides for Fat Loss, Muscle Building & Longevity | Dr. Kyle Gillett MD

Hypoactive sexual desire disorder is a subjective diagnostic category with significant individual and contextual variation; sexual desire appropriateness depends on life circumstances (postpartum period, attempts to conceive, etc.) and partner considerations, so peptide therapy should only be considered after determining whether low desire is truly pathological.

“there is a huge Gray Zone and it also depends on who your partner is so as an example as someone who's had two kids and have also delivered a couple hundred babies I'm familiar with how you might want to have a different sex drive when you're in when your family's in the postpartum period versus when you're trying to get pregnant versus different times in your life so that's something that you should that everybody should talk to their doctor about”

Most GHRP peptides (ghrelin agonists, GHRH analogs, BPC-157, TB-500, GHK copper peptide) lack FDA-approved indications and are used entirely off-label, so when off-label use occurs, clinicians should prioritize compounds with the lowest theoretical risk profiles and the longest histories of clinical use rather than novel compounds.

“by the way bpc157 GHC copper peptide and tb500 are always used off label there's no approved indication whereas for a lot of these classes in fact um approved on label indications yes yes yes yes yes yes but these two do not however theoretically they're some of the lowest risk so whenever there's not an approved indication and it hasn't been through all three stages of clinical trials and gotten approved then you want the theoretical risks to be as low as possible and you also want to be familiar with um how it's been used in the past”

GHRP-induced hyperglycemia occurs independent of increased eating, as evidenced by continuous glucose monitors showing elevated glucose levels throughout the day even when food intake is controlled

“even independent of eating more we know that you do have transient acute hyperglycemia so if you follow it along with your CGM then it's not unusual to see glucose higher throughout the day”

The limbic system contains multiple 'positive switches' required for libido and sexual function—including leptin, alpha-melanocyte-stimulating hormone (α-MSH), and others—and sun exposure increases endogenous α-MSH release from melanocortin receptors, explaining why Brazilians report increased sexual activity during the hottest months.

“within the limbic system there's a lot of different what I call positive switches so in order to have libido you have to have all these switches on and in fact in order to go through puberty you have to have all these switches on leptin is one of the switches so leptin is one of the reasons why when you're very lean um you might have less but a m s h is another one alpha it should be a lowercase Alpha because it's a Greek Alpha msh and this is what normally binds melanocordine receptors”

GHRPs (growth hormone releasing peptides) function through two distinct mechanisms: ghrelin agonists that bind G protein-coupled receptors in the pituitary to stimulate pulsatile growth hormone release, and GHRH analogs that work on a different pituitary receptor, allowing synergistic low-dose combinations that reduce side effects while maintaining efficacy.

“ghrelin binds a g protein coupled receptor in the pituitary and that helps the body release more growth hormone pulsately so it is a growth hormone releasing peptide”

Melanoma risk from melanocortin agonists is contraindicated in people with family history of melanoma, dermatotypes with high intrinsic risk (red hair, freckles, pale skin), or history of 10+ severe sunburns, as these individuals already have significantly elevated melanoma risk.

“if you have any family history of melanoma or if you have a dermatotype for example red hair and a lot of freckles and pale skin significantly increased risk of melanoma or if you've just had a really a lot of really bad sunburns let's say you've had 10 um severe sunburns throughout your life you're also at increased risk of melanoma then I consider that a contraindication for Millennial cord and receptor agonists”

SARMs (Selective Androgen Receptor Modulators) are increasingly progressing through clinical trials for oncological indications, particularly ostarine (MK-2866, rebranded as Enobosarm) for triple-negative androgen receptor-positive breast cancer and prostate cancer, where they inhibit the adrenal androgen synthesis cascade without the systemic virilization of exogenous testosterone.

“ostern which is mk2866 continually progresses forward in the clinical literature when it comes to to what's called Androgen receptor responsive breast cancer which is actually extremely rare it's usually triple negative so er negative PR negative her22 her2 new negative but you think about the benefits of that in an individual who has breast cancer prostate cancer would be the other potential indication”

Clinical trial data for peptides often shows flashing on-and-off benefits because many have only completed Stage 2 or Stage 3 trials without full FDA approval, creating uncertain risk-benefit profiles

“when it comes to um the I guess long-term use of these growth agonists my main concern would be tumor growth I just feel like there's not enough of a um and by the way bpc157 GHC copper peptide and tb500 are always used off label there's no approved indication whereas for a lot of these classes in fact um approved on label indications yes yes yes yes yes yes but these two do not however theoretically they're some of the lowest risk so whenever there's not an approved indication and it hasn't been through all three stages of clinical trials and gotten approved then you want the theoretical risks to be as low as possible”

Pramlintide's poor adherence (three daily injections) limits practical utility compared to lifestyle interventions, making long-acting formulations strategically important for diabetic populations

“this compared to this uh this you're not gonna have good adherence three times a day injections for someone that's not uh if you if you're a type 1 diabetic then perhaps you have good adherence because your life depends on it um but really your life more depends on the insulin”

Contraindications to GHRP use include active tumors (benign or malignant), family history of cancer, and risk of hyperglycemia and insulin resistance, requiring patients to undergo aggressive preventive screening with diagnostic imaging and early cancer detection protocols before initiation.

“part of it depends on if they have a relative contraindication contraindications in my mind would be active tumor benign or malignant chance of an active tumor benign or malignant so they want to have aggressive preventive screening both with Diagnostic Imaging and advanced like early cancer detection and also risk of hyperglycemia and insulin resistance”

Copper deficiency is common after bariatric surgery (gastric bypass or biliary pancreatic diversion) at approximately 10 years post-op, and board-certified bariatricians routinely screen copper levels because deficiency can cause bicytopenia (low white and red blood cells).

“you um that is indeed copper so let's say you've had bariatric surgery and you're not able to absorb copper well about 10 years after gastric bypass or biliary pancreatic diversion it's very common to see deficient copper levels that's why any board-certified obesity medicine physician or bariatrician will check a copper level so that's another thing to watch out for another Fringe benefit or if you have anemia low white blood cells or low red blood cells but you do not have a deficient B12 folate or iron copper is probably another thing you want to check it can cause bicytopenia”

CJC (a GHRH analog) had its clinical trial in Brazil stopped due to a reported death, which is why Gillette personally prefers tessomorelin (Tesamorelin), which has recently received FDA approval for three different indications.

“CJC is one of these I believe it's 12.95. um let's see sir Moreland is another one sir Moreland and then uh sarcotropin is another one there's a whole bunch of ghra analogues and a whole bunch of grelin agonists as well but in general my go-to is Tessa morelin occasionally some Orleans some moreland's been around the longest and it was one of the first to go through this different stages of clinical trials but now is used less just because Tessa Moreland has recently gotten FDA approval I believe for three different indications”

Avastin (bevacizumab), a VEGF-blocking chemotherapy drug, is prescribed because cancers overexpress VEGF and are heavily vascularized; thus, peptides like BPC-157 that increase VEGF and blood flow are contraindicated in anyone with active malignancy because they would feed tumor growth.

“I often mention the medication avastin a-v-a-s-t-i-n which blocks veg F so it's the opposite of bpc157 and it is a essential chemotherapy medication so it's prescribed for many different types of cancers cancers tend to overexpress vegf and they tend to be well vascularized so you don't want to send even more blood flow to something that's so hungry for blood flow that it's growing”

Bremelanotide (PT-141, Vylesi) is FDA-approved only for hypoactive sexual desire disorder in females despite working equally well in males, and it works by activating α-MSH and melanocortin receptors in the limbic system to enhance sexual arousal and spontaneous erections.

“bremelanotide this one uh also known as violisi is indicated for hypoactive sexual disorder whatever that is so that's obviously a very relative thing hypoactive hypoactive sexual disorder and oddly enough um it's only indicated in females although for sure it works on both females and males”

Melanocortan receptor agonists cause side effects including nausea, increased skin tanning and darkening, and loss of photo-bleaching (natural hair lightening) in blonde individuals, but do not cause downregulation or loss of efficacy with continued use.

“it can stop that one sounds kind of kind of interesting nausea is a side effect for all these and in fact for all of these becoming more tan so a darker skin tone and loss of photo bleaching of the hair so if you're like a dirty blonde that has the photo bleaching effect then often you lose that as you start to utilize any of these even the fourth generation which is set melanotide”

Amylin is a peptide co-produced with insulin by pancreatic beta cells and is indicated for treatment of type 1 and type 2 diabetes; synthetic amylin (pramlintide/Symlin) has a very short half-life requiring three daily injections and is weight-negative through potentiation of insulin's glucose-lowering effects.

“amelin is another peptide that's made by the pancreas that's specifically the beta cell so in your pancreas you have your Alpha cell and you have your beta cell these are your Endocrine cells of the pancreas and your islets of langerhans and none of that really matters that much but the takeaway from this is It's indicated in diabetes including type 1 diabetes and it is very weight negative”

Pro-insulin to insulin ratio is a marker of beta-cell dysfunction and impending pancreatic beta-cell death across all diabetes types and severe insulin resistance, even when absolute insulin levels are also elevated

“if you're pro-insulin is high even if you do not have type 1 diabetes if you have type 1.5 or if you have type 2 diabetes or if you just have really severe insulin resistance if your pro insulin is high and your insulin is relatively low compared to that even if it's also High then that is a sign of impending pancreatic death”

TB-500 (thymosin beta 4) and GHK-copper peptide are derived from thymus and liver respectively, and young children heal quickly because they have functional thymi and well-functioning livers, whereas older individuals lack thymic function and hepatic decline—these growth agonists provide targeted benefits similar to systemic growth hormone but with less risk

“thymus in beta 4 comes from the thymus ghk copper peptide comes from the liver they're one reason why say young children with a thymus and a very well functioning liver can heal very quickly whereas older individuals that do not have a thymus and do not have a well-functioning liver cannot so I think of these as more targeted with similar benefits but with less risk than the shotgun approach of increasing growth hormone everywhere”

Oxandrolone (Anavar), despite popular belief, causes hypothalamic-pituitary suppression (shutdown); it is not a consequence-free androgenic compound and should be used judiciously, not casually.

“I've even heard people say there's no shutdown with oxandrolone which is anavar yeah and yes um that also causes hypothalamic and pituitary suppression which is shut down so it's not something that you should take but it's something that you could be excited about”