Possibilities today...Treatments Tomorrow

- NORCAL MEDICAL RESEARCH -

JANUARY/FEBRUARY 2025

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Welcome to the first 2025 NorCal Medical Research Newsletter! It’s an especially exciting time to be conducting clinical trials for persons with the chronic diseases of diabetes, overweight condition, obesity and hypothyroidism. The new GLP-1s and other similar compounds are revolutionizing the way we are approaching obesity, diabetes, and cardiovascular disease (CVD) treatment, reversal AND prevention. The initial impressive results for Ozempic, Mounjaro, Wegovy, Rebelsus and Zepbound have been confirmed in numerous studies showing previously unseen weight loss, reductions in A1C and CVD risks, improvements in sleep apnea and kidney disease and other possible benefits. New clinical trials on GLP-1s are aimed at developing effective combination agents, agents which can be taken in oral forms or by monthly injections and agents which have fewer side effects.That’s progress and due diligence. That’s why we’re doing these clinical trials at NorCal!

Our two new weight loss studies are for individuals who are overweight and also have type 2 diabetes and an A1C >7%. We also expect a number of clinical trials later this spring on some new GLP-1s and other novel glucoregulatory medications to be studied in individuals who do not yet have diabetes but are at risk for diabetes, cardiovascular disease and other diseases because of overweight or obesity. The new GLP-1s being tested will be scrutinized for optimal efficacy, safety and tolerance. If that sounds like you, keep reading!

IF YOUR A1C IS OVER 7 %, that is if your A1C is not at the treatment goal recommended by the 2025 ADA (American Diabetes Association) Standards of Care and you’re frustrated that you can’t lose weight and keep it off, you may qualify for one of the new trials currently enrolling at NorCal right here in the San Francisco North Bay. Our studies will test if the investigational medication may help treat overweight people with type 2 diabetes and an elevated A1C over 7%, not optimally controlled on diet and oral medication, to lose weight and get their A1C to goal.

Glucagon-like peptide 1 (GLP-1) receptor agonists are now recognized by the ADA as a first line treatment for overweight conditions and for lowering A1C to 7% in people with type 2 diabetes. The results of many well-designed trials have clearly proven that getting the A1C to 7% lowers the risks of diabetic eye disease, nerve disease and kidney disease by as much as 50 to 76%!!! And the benefits of getting the A1C to goal of 7% persist for decades. Lowering the A1C to goal of 7% has also been shown to reduce cardiovascular risks such as heart attacks and stroke.

We are also still seeking patients with hypothyroidism for a unique Thyroid Study which compares animal derived thyroid supplement, Armour (combination of T3/T4), to synthetic thyroid hormone, levothyroxine (T4 only), as replacement therapy for individuals who need thyroid supplement. While levothyroxine (T4) remains the standard treatment for hypothyroidism, some patients feel better with a combination therapy of T4 and T3. If you are on T4 alone (levothyroxine), give us a call to find out if this study may be right for you.

There are many reasons why individuals choose to participate as volunteers in a clinical trial including personal benefit as well as contributing importantly to medical knowledge. Remember there is no cost to participants in our clinical trials. Study medications, lab or clinical monitoring are all provided free. There are small stipends for time and travel expenses, and we continue to work with your own physicians and share data if you give permission. (See “What you Give, What You Get”).

So get to know us better at NorCalMedicalResearch.com and contact us at 415-461-1585 or info@norcalmedicalresearch.com with any questions. Follow us on Facebook, LinkedIn and Nextdoor !

Thank you for supporting our mission to improve patient outcomes through careful data gathering and clinical research right here in Greenbrae where we have been actively doing clinical research for almost four decades! Thanks to our readers, the generous participants in our clinical studies and the doctors and friends who have referred patients to us.

Participation in a research study right here in Marin might be an opportunity to focus on improving your health in a new way in 2025, or might help the development of a drug that could benefit you and others worldwide in the future.

We look forward to contributing to a healthier future for all by advancing innovation, by improving patient opportunities and by pursuing excellence in healthcare through clinical research.

Best,

Dr. G

Linda Gaudiani MD FACE FACP

NORCAL Medical Director

- STUDIES NOW ENROLLING -

NEW WEIGHT LOSS STUDIES FOR PERSONS WITH TYPE 2 DIABETES AND ELEVATED A1C

One current diabetes/weight loss study will test a once weekly injectable weight loss medication which is a combination of Tirzepatide (Mounjaro) and LAARA (Long-Acting Amylin Receptor Agonist) to assess changes in A1C and body weight compared to placebo (inactive drug). The study will enroll persons with type 2 diabetes with an elevated A1C over 7% and excess weight. 90% of participants will receive active investigational drug; only 10% will receive placebo.

Another study coming up will test a new oral medication.

You may be eligible to join these studies if you:

have an A1C over 7%
have been diagnosed with Type 2 Diabetes for at least 6 months
are aged 18 to 75 years
are on either no diabetes meds or are on Metformin, with or without an SGLT2 inhibitor.
have not taken part in a clinical researchs study for obesity or overweight in the past year

Please call us! 415-461-1585.

THYROID STUDY

This Study compares purified naturally derived thyroid replacement therapy as Armour thyroid LT3/T4, to synthetic levothyroxine LT4 in individuals with hypothyroidism. Armour is made from purified porcine thyroid and contains both T4 and T3 thyroid hormones.

The study will help determine equivalent doses of LT4 (levothyroxine) and Armour so that individuals can be safely converted from one to the other. All participants will start on Armour thyroid and later will be randomized to receive either LT4 synthetic or Armour T3/T4.Thyroid levels will be closely monitored and thyroid hormone replacement doses will be adjusted to keep thyroid levels optimal throughout the study in everyone.

You may be eligible to participate if you:

are 18 to 75 years of age
are diagnosed with hypothyroidism for at least one year
have had no thyroid surgery within past 12 months
have been on continuous thyroid replacement therapy with LT4 (levothyroxine) for the last 6 months
have had a normal TSH documented in the past year.

The duration of the study is one year.

Participants never have to pay for the study drugs, study visits, or for the procedures or tests that are needed as part of these studies. Patients receive a small stipend for their time and may be reimbursed for approved, study-related travel. All information is shared with your own doctors as requested and is confidential.

Please contact us at 415-461-1585 or info@norcalmedicalresearch.com with questions.

Click here to get acquainted with our physicians

and here to meet the rest of our staff.

From left to right: Dr. Elizabeth Lowe, Dr. Linda Gaudiani, Dr. Irene Teper

- NORCAL KNOWLEDGE NUGGETS -

GLP-1 AGONISTS -

WHAT ARE THEY AND HOW DO THEY WORK?

WHAT ARE GLP-1 AGONISTS?

GLP-1 agonists are a class of medications that were first investigated to help manage blood sugar (glucose) in people with type 2 diabetes. GLP-1 agonists are effective in lowering high blood sugar levels but have also been shown to help treat obesity by several intestinal and neurological pathways. Researchers are still learning about other potential uses and benefits of GLP-1s, but evidence shows that they have impressive cardiovascular benefits, improve heart failure, liver and kidney disease, reduce obstructive sleep apnea and may improve other chronic diseass that significantly impact people’s overall health and quality of life.

NorCal, formerly Marin Endocrine Care and Research, was very involved in the early research trials and development of the first drug in the GLP-1 class, approved and introduced in 2005, as well as many since! The associated weight loss that was noted during the early studies led to a new generation of compounds being used for weight reduction as well as for diabetes. We now appreciate obesity not as a patient failure but as a very complex chronic disease with mutiple causes which can finally be treated successfully in many individuals using a combination of GLP type medications, lifestyle changes focusing on increased physical exercise and dietary change, stress reduction and social support.

The current FDA-approved available GLP-1s are most often weekly injectable medications, but new oral formulations are becoming available and additional improved formulations are now in clinical trials which may provide new treatment options for many patients who cannot tolerate the current formulations.

There is also a similar class of medication called dual GLP-1/GIP receptor agonists (stimulators). Tirzepatide (Mounjaro) is currently on the market and may be even more effective than semaglutide (Ozempic). New versions of all of these drugs are being further studied in combination with other compounds to enhance benefit and tolerability and reduce risks. Results of a 5-year cardiovascular outcome study on tirzepatide in which we participate are close to completion so we will soon know more.

HOW DO GLP-1 AGONISTS WORK?

To understand how GLP-1s work it helps to understand how the naturally occuring GLP-1 hormones work in the body.

GLP-1 is a hormone that the small intestine makes. It has several roles including:

Triggering insulin release from the pancreas: Insulin is an essential hormone that allows the food you eat to enter cells as glucose and be used as fuel, thereby regulating the amount of glucose (sugar) in your blood and allowing normal cell nutrition. If you don't have enough insulin, your blood sugar increases, leading to diabetes and the cells are deprived of nutrition.

Blocking glucagon secretion: Glucagon is a hormone your body uses to raise your blood sugar levels when necessary. By blocking glucagon secretion, GLP-1s prevent excess glucose from going into your bloodstream from this pathway.

Slowing stomach emptying: Slower digestion means slower release of glucose (sugar) and other nutrients from the food you eat into the intestine and into the bloodstream.
Increasing satiety: GLP-1s affect areas of your brain that process hunger and satiety (how full you feel after eating) and other expressions of fullness.

GLP-1 medications work by mimicking naturally occuring GLP-1 hormones. If you have overweight condition, obesity or pre-diabetes or type 2 diabetes, these medications help manage your blood sugar, lower your A1C and enhance weight loss as follows:

by triggering your pancreas to release more insulin
by slowing digestion which also helps decrease blood sugar spikes
by increasing the feeling of satiety (fullness) which reduces your food intake, appetite and hunger, often resulting in weight loss.

WHEN WOULD I NEED TO TAKE A GLP-1 AGONIST?

Healthcare providers prescribe GLP-1s for type 2 diabetes and obesity.

GLP-1s for Type 2 Diabetes

The FDA approved the use of GLP-1s to help manage type 2 diabetes (T2D) because they help lower your A1C. An A1C test measures the average amount of sugar in your blood over the past few months. There are a few conditions in which the A1C may not reflect the actual average glucose control for example in anemia, renal disease and other variations in hemoglobin but physicians know to evaluate for these discrepancies. In population data overall A1C correlates closely with diabetes complications and so lowering the A1C to goal is still recommended by the ADA (Amercian Diabetes Association) and is the best way to lower the risk of diabetes complications. Healthcare providers use the A1C to help diagnose pre-diabetes and type 2 diabetes and to monitor how well your diabetes treatment plan is working.

There are several other types of diabetes medications including metformin, which are often used as the first medications for treating type 2 diabetes. Your healthcare provider may recommend a GLP-1 agonist if:

metformin is not helping manage T2D
if it's unsafe for you to take metformin due to side effects of kidney insufficiency
you have an A1C higher than your target
you haven't reached your target A1C within 3 months of treatment and you have additional conditions, like atherosclerosis, heart failure or chronic kidney disease
if you are overweight

Our current GLP-1 clinical studies may be right for you if your A1C is higher than 7%. See above for more information.

It's important to remember that the most effective management of T2D usually involves several therapies and medications, permanent lifestyle and dietary modifications, regular exercise, improved sleep and stress reduction but weight management is key.

GLP-1's for Obesity

The FDA currently approves the use of semaglutide and high-dose liraglutide and tirzepatide to help treat obesity. Health care providers may also prescribe these medications for people who have overweight along with other health conditions since losing weight can help manage coexisting conditions. Sometimes insurance covers these medications but often they do not.

We will have GLP-1 weight loss studies later in the year for persons without diabetes, please stay tuned! One of them may be right for you!

WHAT ABOUT THE SIDE EFFECTS?

Just a few years after some TikTok videos spiked the demand it is thought that one in eight US adults has tried Ozempic or another drug in its class! In the early days of social media craze, some patients reported severe gastrointestinal side effects and there are still some 30% or more of patients who stop medications because of intolerance. Research shows that while many patients do experience side effects today, they are usually at a mild to moderate level while the dosage increases, and the unpleasantness tapers with time. Tolerance can depend on how well patients are instructed about how to take these medications correctly.

When healthcare providers have in-depth conversations with their patients before they write the first prescription, they set the stage for success from the beginning. It is important for them to explain to patients that side effects, most commonly nausea, diarrhea, constipation and vomiting, tend to subside over time. After the third or fourth injection, many patients improve and perhaps have no side effects at all.

Close medical monitoring is extremely important to patient safety and success. Health care providers need to counsel patients to avoid triggers for adverse reactions such as certain types of foods, large portion size, and speed of eating.

When you consider the many known benefits of blood sugar management, weight loss, improved exercise tolerance, lower risk of high blood pressure, heart disease, stroke, sleep apnea, metabolic syndrome, fatty liver disease, several cancers and more, the advantages of GLP-1s seem worthwhile.

BENEFITS OF PARTICIPATING IN A CLINICAL TRIAL

Participants in well conducted clinical trials may benefit from the investigational product itself, as well as from the nutritional, exercise and lifestyle counselling that may be part of the protocol. No medical insurance is required, and personal identity and results are highly protected by codes. There is no cost at all to a participant in a clinical research study. Labs, medical visits, monitoring, and study drugs are free, and stipends are provided for patient travel and time. Protocols are very carefully explained to interested persons as well as the possibility of receiving placebo (inactive comparators) in some study protocols as part of Informed Consent procedures. Investigator physicians can communicate results and progress with primary care doctors as requested.

WHAT DO WE STILL NEED TO KNOW ABOUT GLP-1'S THAT WE MIGHT FIND OUT FROM CLINICAL STUDIES?

How durable are the results and what will happen if people discontinue use after some time?
How about the results from combinations of GLP-1 meds with other glucoregulatory hormones that have since been discovered like GIPR, glucagon, amylin and others. Will they yield even better results? Will the side effects be reduced?
Can we develop safe and effective oral preparations?
What is the long-term safety profile of these preparations? Will they be found to have serious adverse events over time?
Can new formulations improve tolerability, especially reducing the gastrointestinal side effects that some 30-50% of people experience on these meds?
What about preservation of lean body mass and avoidance of muscle wasting (sarcopenia)?
Will this group of drugs be useful to treat other conditions, like addictions, neurologic diseases?
What about safety in other populations, children, adolescents, the elderly, hospitalized persons?
Are cheaper compounded products effective? Safe?

SOURCE:

Cleveland Clinic - GLP-1 Agonists - https://my.clevelandclinic.org/health/treatments/13901-glp-1-agonists

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